| Type |
Details |
Score |
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
82
 |
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
296
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
20
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
152
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
227
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
374
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
183
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
84
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
175
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
170
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
76
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
130
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
69
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
697
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
135
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
302
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
223
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
288
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
54
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hunt LT |
| Year: |
1989 |
| Journal: |
FASEB J |
| Title: |
Avidin-like domain in an epidermal growth factor homolog from a sea urchin. |
| Volume: |
3 |
| Issue: |
6 |
| Pages: |
1760-4 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Pugliese L |
| Year: |
1993 |
| Journal: |
J Mol Biol |
| Title: |
Three-dimensional structure of the tetragonal crystal form of egg-white avidin in its functional complex with biotin at 2.7 A resolution. |
| Volume: |
231 |
| Issue: |
3 |
| Pages: |
698-710 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Green NM |
| Year: |
1990 |
| Journal: |
Methods Enzymol |
| Title: |
Avidin and streptavidin. |
| Volume: |
184 |
|
| Pages: |
51-67 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hendrickson WA |
| Year: |
1989 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation. |
| Volume: |
86 |
| Issue: |
7 |
| Pages: |
2190-4 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Vinogradova O |
| Year: |
2002 |
| Journal: |
Cell |
| Title: |
A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face. |
| Volume: |
110 |
| Issue: |
5 |
| Pages: |
587-97 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Foley SF |
| Year: |
2003 |
| Journal: |
Eur J Biochem |
| Title: |
The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. Functional and structural insights through disulfide structure analysis. |
| Volume: |
270 |
| Issue: |
17 |
| Pages: |
3610-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Calvanese L |
| Year: |
2009 |
| Journal: |
J Pept Sci |
| Title: |
Structural insights into the interaction between the Cripto CFC domain and the ALK4 receptor. |
| Volume: |
15 |
| Issue: |
3 |
| Pages: |
175-83 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lijnen HR |
| Year: |
2001 |
| Journal: |
Ann N Y Acad Sci |
| Title: |
Elements of the fibrinolytic system. |
| Volume: |
936 |
|
| Pages: |
226-36 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hucthagowder V |
| Year: |
2006 |
| Journal: |
Am J Hum Genet |
| Title: |
Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome. |
| Volume: |
78 |
| Issue: |
6 |
| Pages: |
1075-80 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Dasouki M |
| Year: |
2007 |
| Journal: |
Am J Med Genet A |
| Title: |
Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa. |
| Volume: |
143A |
| Issue: |
22 |
| Pages: |
2635-41 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hoyer J |
| Year: |
2009 |
| Journal: |
Clin Genet |
| Title: |
Lethal cutis laxa with contractural arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation. |
| Volume: |
76 |
| Issue: |
3 |
| Pages: |
276-81 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Le Gat L |
| Year: |
2001 |
| Journal: |
Cell Commun Adhes |
| Title: |
Prominent beta-5 gene expression in the cardiovascular system and in the cartilaginous primordiae of the skeleton during mouse development. |
| Volume: |
8 |
| Issue: |
3 |
| Pages: |
99-112 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Norledge BV |
| Year: |
2003 |
| Journal: |
Proteins |
| Title: |
The tissue factor/factor VIIa/factor Xa complex: a model built by docking and site-directed mutagenesis. |
| Volume: |
53 |
| Issue: |
3 |
| Pages: |
640-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lapecorella M |
| Year: |
2008 |
| Journal: |
Haemophilia |
| Title: |
Factor VII deficiency: defining the clinical picture and optimizing therapeutic options. |
| Volume: |
14 |
| Issue: |
6 |
| Pages: |
1170-5 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Vadivel K |
| Year: |
2012 |
| Journal: |
Front Biosci (Landmark Ed) |
| Title: |
Structural biology of factor VIIa/tissue factor initiated coagulation. |
| Volume: |
17 |
|
| Pages: |
2476-94 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Reverter D |
| Year: |
2004 |
| Journal: |
J Mol Biol |
| Title: |
Crystal structure of human carboxypeptidase M, a membrane-bound enzyme that regulates peptide hormone activity. |
| Volume: |
338 |
| Issue: |
2 |
| Pages: |
257-69 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Tan F |
| Year: |
2003 |
| Journal: |
Biochem J |
| Title: |
Effect of mutation of two critical glutamic acid residues on the activity and stability of human carboxypeptidase M and characterization of its signal for glycosylphosphatidylinositol anchoring. |
| Volume: |
370 |
| Issue: |
Pt 2 |
| Pages: |
567-78 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Deiteren K |
| Year: |
2007 |
| Journal: |
Biochim Biophys Acta |
| Title: |
The role of the S1 binding site of carboxypeptidase M in substrate specificity and turn-over. |
| Volume: |
1774 |
| Issue: |
2 |
| Pages: |
267-77 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Marquez-Curtis L |
| Year: |
2008 |
| Journal: |
Stem Cells |
| Title: |
Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization? |
| Volume: |
26 |
| Issue: |
5 |
| Pages: |
1211-20 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Zhang X |
| Year: |
2008 |
| Journal: |
J Biol Chem |
| Title: |
Carboxypeptidase M and kinin B1 receptors interact to facilitate efficient b1 signaling from B2 agonists. |
| Volume: |
283 |
| Issue: |
12 |
| Pages: |
7994-8004 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Zhou MM |
| Year: |
1995 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor. |
| Volume: |
92 |
| Issue: |
17 |
| Pages: |
7784-8 |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
The netrin (NTR) module is an about 130-residue domain found in the C-terminal parts of netrins, complement proteins C3, C4, and C5, secreted frizzled-related proteins, and type I procollagen C-proteinase enhancer proteins (PCOLCEs), as well as in the N-terminal parts of tissue inhibitors of metalloproteinases (TIMPs). The proteins harboring the NTR domain fulfill diverse biological roles ranging from axon guidance, regulation of Wnt signalling, to the control of the activity of metalloproteinases. The NTR domain can be found associated to other domains such as CUB, WAP, Kazal, Kunitz, Ig-like, laminin N-terminal, laminin-type EGF or frizzled. The NTR domain is implicated in inhibition of zinc metalloproteinases of the metzincin family [, ].The NTR module is a basic domain containing six conserved cysteines, which are likely to form internal disulphide bonds, and several conserved blocks of hydrophobic residues (including an YLLLG-like motif). The NTR module consists of a β-barrel with two terminal α-helices packed side by side against the face of the β-barrel (see ) [].This entry includes most netrin modules, but excludes those found in TIMPs. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF) has been shown [, , , ]to be present, in a more or less conserved form, in a large number of other, mostly animal, proteins. EGF is a polypeptide of about 50 amino acids with three internal disulfide bridges. It first binds with high affinity to specific cell-surface receptors and then induces their dimerization, which is essential for activating the tyrosine kinase in the receptor cytoplasmic domain, initiating a signal transduction that results in DNA synthesis and cell proliferation.A common feature of all EGF-like domains is that they are found in the extracellular domain of membrane-bound proteins or in proteins known to besecreted (exception: prostaglandin G/H synthase). The EGF-like domain includes six cysteine residues which have been shown to be involved in disulfide bonds. The structure of several EGF-like domains has been solved. The fold consists of two-stranded β-sheet followed by a loop to a C-terminal shorttwo-stranded sheet. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Sorting nexins (SNXs) are a diverse group of cellular trafficking proteins that are unified by the presence of a phospholipid-binding motif, the PX domain. The ability of these proteins to bind specific phospholipids, as well as their propensity to form protein-protein complexes, points to a role for these proteins in membrane trafficking and protein sorting []. Members of this group also contain coiled-coil regions within their large C-terminal domains and a BAR domain, whose function has been defined as a dimerisation motif, as sensing and inducing membrane curvature, and/or likely to bind to small GTPases [].This entry includes SNX5, SNX6 and SNX32 (also known as SNX6B).SNX5 contains a BAR domain that is C teminus to the PX domain. SNX5 plays a role in macropinocytosis []and in the internalisation of EGFR after EGF stimulation [].SNX6 was found to interact with members of the transforming growth factor-beta family of receptor serine/threonine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivoof oligomeric complexes. SNX6 is localized in the cytoplasm where it is thought to target proteins to the trans-Golgi network []. In addition, SNX6 was found to be translocated from the cytoplasm to nucleus by Pim-1, an oncogene product of serine/threonine kinase. This translocation is not affected by Pim-1-dependent phosphorylation, but the functional significance is unknown []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Laminin is a large molecular weight glycoprotein present only in basementmembranes in almost every animal tissue. Each laminin is a heterotrimerassembled from alpha, beta and gamma chain subunits, secreted and incorporatedinto cell-associated extracellular matrices. The laminins can self-assemble,bind to other matrix macromolecules, and have unique and shared cellinteractions mediated by integrins, dystroglycan, and other receptors. Throughthese interactions, laminins critically contribute to cell differentiation,shape and movement, maintenance of tissue phenotypes,and promotion of tissuesurvival [, ].The different laminin chains share a 600-residue domain I/II whicholigomerises into a rod-like coiled-coil structure forming the long arm oflaminins. The N-terminal short arms consist of rod-like elements (domain IIIand V) formed by tandem arrays of laminin-type EGF modulesand several globular domains: domains IV and domain VI (lamininN-terminal). All alpha chains share a unique C-terminal Gdomain which consists of five laminin G modules []. Laminin IV domain is also found in the perlecan protein, an integral component ofbasement membranes, which serves also as an attachment substrate for cells,but it is not found in short laminin chains (alpha4 or beta3). The function ofthis domain is not yet known. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [, ]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits []. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.Some receptors share a common beta chain while having different alpha chains [, ]. A number of different beta chains, beta-1 to beta-8 are known in higher eukaryotes.This entry represents the family of integrin beta subunit proteins. It also includes integrin beta-like protein 1, whose function is unknown. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Fibulins are a family of ECM glycoproteins characterized by a fibulin-type C-terminal domain preceded by tandem calcium-binding epidermal growth factor (EGF)-like modules. They are involved in protein-protein interaction with the components of basement membrane and extracellular matrix proteins. There are five fibulins, which can be classified into two subgroups. Fibulin-1 and -2 constitute one subgroup. These fibulins are larger than the others due to the presence of a higher number of EGF modules and an extra domain with three anaphylatoxin modules []. Members of the second subgroup, fibulin-3, -4, and -5, are similarly small in size and highly homologous to one another in modular structure. They consist of a modified cbEGF domain at the N terminus followed by five tandem cbEGF modules and the fibulin-type C-terminal region.This entry represents EGF-containing fibulin-like extracellular matrix protein 2 (Efemp2), also known as fibulin-4. Efemp2 binds to tropoelastin and may play an important role in the assembly of elastic fibres during development []. Defects in Efemp2 cause autosomal recessive cutis laxa, an heterogeneous group of connective tissue disorders characterised by cutaneous abnormalities and variable systemic manifestations such as loose skin. In addition to skin, internal organs enriched in elastic fibres, such as the lung and the arteries, are alsoaffected [, , ]. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [, ]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits []. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.This entry represents the cytoplasmic domain of integrin beta subunits []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Factor VII (F7) initiates the extrinsic pathway of blood coagulation. It contains an N-terminal Gla domain followed by two epidermal growth factor-like domains (EGF1 and EGF2) and a C-terminal trypsin-like serine protease domain. It can be transformed into active forms (FVIIa) by proteolytic cleavage of the activation peptide located in the connecting region between the EGF2 and the protease domain; this results in the formation of a two-chain FVIIa molecule and a heavy chain held together by a single disulfide bond []. Its first EGF domain (EGF1) binds a calcium ion at its N terminus [].At an injury site, initiation of coagulation begins by exposure of blood to tissue factor (TF) in the extravascular space and formation of the Ca2+-dependent complex between TF and plasma FVIIa. The Ca2+/FVIIa/TF complex formed on the cell surfaces then activates both FX and FIX leading to thrombin generation and fibrin formation []. Mutations in the F7 gene cause Factor VII deficiency (FA7D), the most frequent among rare congenital bleeding disorders []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
The Notch domain is also called the 'DSL' domain or the Lin-12/Notch repeat (LNR). The LNR region is present only in Notch related proteins C-terminal to EGF repeats. The lin-12/Notch proteins act as transmembrane receptors for intercellular signals that specify cell fates during animal development. In response to a ligand, proteolytic cleavages release the intracellular domain of Notch, which then gains access to the nucleus and acts as a transcriptional co-activator []. The LNR region is supposed to negatively regulate the Lin-12/Notch proteins activity. It is a triplication of an around 35-40 amino acids module present on the extracellular part of the protein [, ]. Each module contains six cysteine residues engaged in three disulphide bonds and three conserved aspartate and asparagine residues []. The biochemical characterisation of a recombinantly expressed LIN-12.1 module from the human Notch1 receptor indicate that the disulphide bonds are formed between the firstand fifth, second and fourth, and third and sixth cysteines. The formation of this particular disulphide isomer is favored by the presence of Ca2+,which is also required to maintain the structural integrity of the rLIN-12.1 module. The conserved aspartate and asparagine residues are likely to be important for Ca2+binding, and thereby contribute to the native fold. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
The SH2-containing Shc adapter proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to the Ras/mitogen-activated protein kinase (MAPK) pathway []. Three Shc genes were originally identified in mammals that encode proteins characterised by an amino-terminal phosphotyrosine binding (PTB) domain and a carboxy-terminal Src homology 2 domain. Shc1 (ShcA) is ubiquitously expressed, whereas expression of Shc2 (ShcB) and Shc3 (ShcC) appears to be limited to neuronal cells [].SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation []. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites [, , ]. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Carboxypeptidase M (CPM; MEROPS identifier M14.006; ) is an extracellular glycoprotein, bound to cell membranes via a glycosyl-phosphatidylinositol on the C terminus of the protein []. It specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins [, ]. The highest levels of CPM have been found in human lung and placenta, but significant amounts are present in kidney, blood vessels, intestine, brain, and peripheral nerves. CPM has also been found in soluble form in various body fluids, including amniotic fluid, seminal plasma and urine. Due to its wide distribution in a variety of tissues, it is believed that it plays an important role in the control of peptide hormones and growth factor activity on the cell surface and in the membrane-localized degradation of extracellular proteins. For example, it hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. CPM is a required processing enzyme that generates specific agonists for the B1 receptor [, ].This entry represents the carboxypeptidase (N-terminal) domain of carboxypeptidase M. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Avidin []is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that is extremely difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin.Avidin and streptavidin both form homotetrameric complexes of noncovalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin. The three-dimensional structures of both streptavidin [, ]and avidin []have been determined and revealed them to share a common fold: an eight stranded anti-parallel β-barrel with a repeated +1 topology enclosing an internal ligand binding site.Fibropellins I and III []are proteins that form the apical lamina of the sea urchin embryo, a component of the extracellular matrix. These two proteins have a modular structure composed of a CUB domain (see), followed by a variable number of EGF repeats and a C-terminal avidin-like domain. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents the CFC domain found in the membrane protein Cripto (or teratocarcinoma-derived growth factor), a protein over expressed in many tumours [, ]and structurally similar to the C-terminal extracellular portions of Jagged 1 and Jagged 2 []. CFC is approx 40-residues long, compacted by three internal disulphide bridges, and binds Alk4 via a hydrophobic patch. CFC is structurally homologous to the VWFC-like domain []. The protein Cripto is the founding member of the extra-cellular EGF-CFC growth factors, which are composed of two adjacent cysteine-rich domains: the EGF-like and the CFC domains. Members of the EGF-CFC family play key roles in embryonic development and are also implicated in tumourigenesis []. The Cripto protein could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm. Although both the EGF and CFC domains are involved in the tumourigenic activity of Crispto proteins, the CFC domain appears to play a crucial role, as it is through the CFC domain that Crispto interferes with the onco-suppressive activity of Activins, either by blocking the Activin receptor ALK4 or by antagonising proteins of the TGF-beta family []. The Cryptic protein is involved in the correct establishment of the left-right axis. May play a role in mesoderm and/or neural patterning during gastrulation. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [, ]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits []. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.This superfamily represent the C-terminal domain of integrin alpha (which can be further subdivided in the thight, calf-1 and calf-2 domains) and the central region of integrin beta known as the hybrid domain []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Avidin []is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that is extremely difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin.Avidin and streptavidin both form homotetrameric complexes of noncovalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin. The three-dimensional structures of both streptavidin [, ]and avidin []have been determined and revealed them to share a common fold: an eight stranded anti-parallel β-barrel with a repeated +1 topology enclosing an internal ligand binding site.Fibropellins I and III []are proteins that form the apical lamina of the sea urchin embryo, a component of the extracellular matrix. These two proteins have a modular structure composed of a CUB domain (see), followed by a variable number of EGF repeats and a C-terminal avidin-like domain. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Avidin []is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that is extremely difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin.Avidin and streptavidin both form homotetrameric complexes of noncovalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin. The three-dimensional structures of both streptavidin [, ]and avidin []have been determined and revealed them to share a common fold: an eight stranded anti-parallel β-barrel with a repeated +1 topology enclosing an internal ligand binding site.Fibropellins I and III []are proteins that form the apical lamina of the sea urchin embryo, a component of the extracellular matrix. These two proteins have a modular structure composed of a CUB domain (see), followed by a variable number of EGF repeats and a C-terminal avidin-like domain. |
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| Protein Domain |
| Type: |
Conserved_site |
| Description: |
Avidin []is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that is extremely difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin. Avidin and streptavidin both form homotetrameric complexes of noncovalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin.The three-dimensional structures of both streptavidin [, ]and avidin []have been determined and revealed them to share a common fold: an eightstranded anti-parallel β-barrel with a repeated +1 topology enclosing aninternal ligand binding site.Fibropellins I and III []are proteins that form the apical lamina of the seaurchin embryo, a component of the extracellular matrix. These two proteinshave a modular structure composed of a CUB domain (see), followedby a variable number of EGF repeats and a C-terminal avidin-like domain. This entry represents this avidin-like domain. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [, ]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits []. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.Integrin beta-5 associates with alpha-V. It is a key integrin involved in angiogenesis, vasculogenesis, hematopoiesis and bone formation []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [, ]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits []. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.Integrin Beta-6 associates with Alpha-V to form the receptor for the TGFB1 latency-associated peptide (LAP) []. Cells expressing this integrin combination induce spatially restricted activation of TGFB1, while mice lacking the integrin display exaggerated inflammation and are protected from pulmonary fibrosis. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [, ]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits []. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.The Integrin beta-8 subunit is a 95kDa glycosylated polypeptide that is typical of other beta chain integrins. It associates with the Alpha-V chain and this heterodimer is found in mature synapses of mouse and rat brains. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Laminin is a large molecular weight glycoprotein present only in basement membranes in almost every animal tissue. Each laminin is a heterotrimer assembled from alpha, beta and gamma chain subunits, secreted and incorporated into cell-associated extracellular matrices. The laminins can self-assemble, bind to other matrix macromolecules, and have unique and shared cell interactions mediated by integrins, dystroglycan, and other receptors. Through these interactions, laminins critically contribute to cell differentiation, shape and movement, maintenance of tissue phenotypes, and promotion of tissue survival [, ]. The different laminin chains share a 600-residue domain I/II which oligomerizes into a rod-like coiled-coil structure forming the long arm of laminins. The N-terminal short arms consist of rod-like elements (domain III and V) formed by tandem arrays of laminin-type EGF modules and several globular domains: domains IV and domain VI (laminin N-terminal). All alpha chains share a unique C-terminal G domain which consists of five laminin G modules []. Laminin IV domain is also found in the perlecan protein, an integral component of basement membranes, which also serves as an attachment substrate for cells, but it is not found in short laminin chains (alpha4 or beta3). The function of this domain is not yet known. The domain IV of laminin beta chains displays no sequence homology to other laminin IV domains. This entry represents this atypical domain IV. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Fibulins are a family of ECM glycoproteins characterized by a fibulin-type C-terminal domain preceded by tandem calcium-binding epidermal growth factor (EGF)-like modules. They are involved in protein-protein interaction with the components of basement membrane and extracellular matrix proteins. There are five fibulins, which can be classified into two subgroups. Fibulin-1 and -2 constitute one subgroup. These fibulins are larger than the others due to the presence of a higher number of EGF modules and an extra domain with three anaphylatoxin modules []. Members of the second subgroup, fibulin-3, -4, and -5, are similarly small in size and highly homologous to one another in modular structure. They consist of a modified cbEGF domain at the N terminus followed by five tandem cbEGF modules and the fibulin-type C-terminal region.Fibulin-2 is the largest of all the fibulins, because it possesses an additional N-terminal domain not found in other fibulins. Fibulin-2 and fibulin-1 overlap in their binding patterns, which ligands that include fibronectin, proteoglycans, tropoelastin, and various elastic fibre and basement membrane proteins. Only a couple of ligands are specific for fibulin-1 (fibrinogen and laminin-1) and for fibulin-2 (fibrillin-1 and perlecan) []. Expression of the fibulin-2 initiates later than fibulin-1 during embryonic development and is distributed in a more restricted manner. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The Notch domain is also called the 'DSL' domain or the Lin-12/Notch repeat (LNR). The LNR region is present only in Notch related proteins C-terminal to EGF repeats. The lin-12/Notch proteins act as transmembrane receptors for intercellular signals that specify cell fates during animal development. In response to a ligand, proteolytic cleavages release the intracellular domain of Notch, which then gains access to the nucleus and acts as a transcriptional co-activator []. The LNR region is supposed to negatively regulate the Lin-12/Notch proteins activity. It is a triplication of an around 35-40 amino acids module present on the extracellular part of the protein [, ]. Each module contains six cysteine residues engaged in three disulphide bonds and three conserved aspartate and asparagine residues []. The biochemical characterisation of a recombinantly expressed LIN-12.1 module from the human Notch1 receptor indicate that the disulphide bonds are formed between the firstand fifth, second and fourth, and third and sixth cysteines. The formation of this particular disulphide isomer is favored by the presence of Ca2+, which is also required to maintain the structural integrity of the rLIN-12.1 module. The conserved aspartate and asparagine residues are likely to be important for Ca2+binding, and thereby contribute to the native fold. |
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| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
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| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
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| GO Term |
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| GO Term |
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| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
787
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| Fragment?: |
false |
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| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
806
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| Fragment?: |
false |
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| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
787
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| Fragment?: |
false |
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| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
112
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| Fragment?: |
true |
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| Publication |
| First Author: |
Springer TA |
| Year: |
1998 |
| Journal: |
J Mol Biol |
| Title: |
An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components. |
| Volume: |
283 |
| Issue: |
4 |
| Pages: |
837-62 |
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•
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| Publication |
| First Author: |
Brown MS |
| Year: |
1986 |
| Journal: |
Science |
| Title: |
A receptor-mediated pathway for cholesterol homeostasis. |
| Volume: |
232 |
| Issue: |
4746 |
| Pages: |
34-47 |
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•
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| Publication |
| First Author: |
Davis CG |
| Year: |
1987 |
| Journal: |
Nature |
| Title: |
Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. |
| Volume: |
326 |
| Issue: |
6115 |
| Pages: |
760-5 |
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•
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| Publication |
| First Author: |
May P |
| Year: |
2007 |
| Journal: |
Ann Med |
| Title: |
The LDL receptor-related protein (LRP) family: an old family of proteins with new physiological functions. |
| Volume: |
39 |
| Issue: |
3 |
| Pages: |
219-28 |
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•
•
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| Publication |
| First Author: |
Elenius K |
| Year: |
1999 |
| Journal: |
Oncogene |
| Title: |
Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. |
| Volume: |
18 |
| Issue: |
16 |
| Pages: |
2607-15 |
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•
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| Publication |
| First Author: |
Oh YS |
| Year: |
2011 |
| Journal: |
PLoS One |
| Title: |
Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors. |
| Volume: |
6 |
| Issue: |
8 |
| Pages: |
e23894 |
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•
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| Publication |
| First Author: |
Wang Y |
| Year: |
2005 |
| Journal: |
J Biol Chem |
| Title: |
Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. |
| Volume: |
280 |
| Issue: |
18 |
| Pages: |
18341-7 |
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•
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| Publication |
| First Author: |
Suen KL |
| Year: |
1993 |
| Journal: |
Mol Cell Biol |
| Title: |
Molecular cloning of the mouse grb2 gene: differential interaction of the Grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors. |
| Volume: |
13 |
| Issue: |
9 |
| Pages: |
5500-12 |
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•
•
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| Publication |
| First Author: |
Laurikkala J |
| Year: |
2001 |
| Journal: |
Dev Biol |
| Title: |
TNF signaling via the ligand-receptor pair ectodysplasin and edar controls the function of epithelial signaling centers and is regulated by Wnt and activin during tooth organogenesis. |
| Volume: |
229 |
| Issue: |
2 |
| Pages: |
443-55 |
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•
•
•
•
|
| Publication |
| First Author: |
Gao L |
| Year: |
2013 |
| Journal: |
Hepatology |
| Title: |
Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver regeneration in mice. |
| Volume: |
57 |
| Issue: |
5 |
| Pages: |
1992-2003 |
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•
•
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| Publication |
| First Author: |
Dail M |
| Year: |
2004 |
| Journal: |
J Biol Chem |
| Title: |
SHEP1 function in cell migration is impaired by a single amino acid mutation that disrupts association with the scaffolding protein cas but not with Ras GTPases. |
| Volume: |
279 |
| Issue: |
40 |
| Pages: |
41892-902 |
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•
•
•
|
| Publication |
| First Author: |
Di Stefano P |
| Year: |
2004 |
| Journal: |
Mol Biol Cell |
| Title: |
P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein involved in cell spreading. |
| Volume: |
15 |
| Issue: |
2 |
| Pages: |
787-800 |
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•
•
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| Publication |
| First Author: |
Weller A |
| Year: |
1991 |
| Journal: |
J Cell Biol |
| Title: |
Amino acid sequence of mouse tenascin and differential expression of two tenascin isoforms during embryogenesis. |
| Volume: |
112 |
| Issue: |
2 |
| Pages: |
355-62 |
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•
•
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| Publication |
| First Author: |
Lawson J |
| Year: |
2002 |
| Journal: |
Biochim Biophys Acta |
| Title: |
Genomic structure and promoter characterization of the gene encoding the ErbB ligand betacellulin. |
| Volume: |
1576 |
| Issue: |
1-2 |
| Pages: |
183-90 |
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•
•
•
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| Publication |
| First Author: |
Miles LA |
| Year: |
2018 |
| Journal: |
J Thromb Haemost |
| Title: |
The plasminogen receptor, Plg-RKT, is essential for mammary lobuloalveolar development and lactation. |
| Volume: |
16 |
| Issue: |
5 |
| Pages: |
919-932 |
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•
•
•
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| Publication |
| First Author: |
Shirayoshi Y |
| Year: |
1997 |
| Journal: |
Genes Cells |
| Title: |
Proto-oncogene of int-3, a mouse Notch homologue, is expressed in endothelial cells during early embryogenesis. |
| Volume: |
2 |
| Issue: |
3 |
| Pages: |
213-24 |
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•
•
•
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| Publication |
| First Author: |
Haft CR |
| Year: |
1998 |
| Journal: |
Mol Cell Biol |
| Title: |
Identification of a family of sorting nexin molecules and characterization of their association with receptors. |
| Volume: |
18 |
| Issue: |
12 |
| Pages: |
7278-87 |
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•
•
•
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| Publication |
| First Author: |
Amin AH |
| Year: |
2010 |
| Journal: |
Lab Invest |
| Title: |
Modified multipotent stromal cells with epidermal growth factor restore vasculogenesis and blood flow in ischemic hind-limb of type II diabetic mice. |
| Volume: |
90 |
| Issue: |
7 |
| Pages: |
985-96 |
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•
•
•
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| Publication |
| First Author: |
Eyermann CE |
| Year: |
2021 |
| Journal: |
Cell Death Dis |
| Title: |
ΔN63 suppresses the ability of pregnancy-identified mammary epithelial cells (PIMECs) to drive HER2-positive breast cancer. |
| Volume: |
12 |
| Issue: |
6 |
| Pages: |
525 |
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•
•
•
•
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| Publication |
| First Author: |
Alferez D |
| Year: |
2008 |
| Journal: |
Mol Cancer Ther |
| Title: |
Dual inhibition of VEGFR and EGFR signaling reduces the incidence and size of intestinal adenomas in Apc(Min/+) mice. |
| Volume: |
7 |
| Issue: |
3 |
| Pages: |
590-8 |
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•
•
•
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| Publication |
| First Author: |
Bashir O |
| Year: |
2003 |
| Journal: |
Clin Sci (Lond) |
| Title: |
Effect of epidermal growth factor administration on intestinal cell proliferation, crypt fission and polyp formation in multiple intestinal neoplasia (Min) mice. |
| Volume: |
105 |
| Issue: |
3 |
| Pages: |
323-30 |
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•
•
•
•
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| Publication |
| First Author: |
Liu X |
| Year: |
2014 |
| Journal: |
Biol Reprod |
| Title: |
Multiple pathways mediate luteinizing hormone regulation of cGMP signaling in the mouse ovarian follicle. |
| Volume: |
91 |
| Issue: |
1 |
| Pages: |
9 |
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•
•
•
•
|
| Publication |
| First Author: |
Apostolakis EM |
| Year: |
2000 |
| Journal: |
Mol Endocrinol |
| Title: |
Epidermal growth factor activates reproductive behavior independent of ovarian steroids in female rodents. |
| Volume: |
14 |
| Issue: |
7 |
| Pages: |
1086-98 |
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•
•
•
•
|
| Publication |
| First Author: |
Panigone S |
| Year: |
2008 |
| Journal: |
Mol Endocrinol |
| Title: |
Luteinizing hormone signaling in preovulatory follicles involves early activation of the epidermal growth factor receptor pathway. |
| Volume: |
22 |
| Issue: |
4 |
| Pages: |
924-36 |
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•
•
•
•
|
| Publication |
| First Author: |
Wiesen JF |
| Year: |
1999 |
| Journal: |
Development |
| Title: |
Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. |
| Volume: |
126 |
| Issue: |
2 |
| Pages: |
335-44 |
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•
•
•
•
|
| Publication |
| First Author: |
Gallego MI |
| Year: |
2001 |
| Journal: |
Dev Biol |
| Title: |
Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. |
| Volume: |
229 |
| Issue: |
1 |
| Pages: |
163-75 |
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•
•
•
•
|
| Publication |
| First Author: |
MacRae Dell K |
| Year: |
2004 |
| Journal: |
Kidney Int |
| Title: |
EGF-related growth factors in the pathogenesis of murine ARPKD. |
| Volume: |
65 |
| Issue: |
6 |
| Pages: |
2018-29 |
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•
•
•
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| Publication |
| First Author: |
Xian CJ |
| Year: |
2001 |
| Journal: |
Exp Neurol |
| Title: |
Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms. |
| Volume: |
172 |
| Issue: |
1 |
| Pages: |
182-8 |
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•
•
•
•
|
| Publication |
| First Author: |
Madtes DK |
| Year: |
1999 |
| Journal: |
Am J Respir Cell Mol Biol |
| Title: |
Transforming growth factor-alpha deficiency reduces pulmonary fibrosis in transgenic mice. |
| Volume: |
20 |
| Issue: |
5 |
| Pages: |
924-34 |
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