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2  structures 28  species 0  interactions 53  sequences 11  architectures

Family: Ig_Tie2_1 (PF10430)

Summary: Tie-2 Ig-like domain 1

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Tie-2 Ig-like domain 1 Provide feedback

No Pfam abstract.

Literature references

  1. Macdonald PR, Progias P, Ciani B, Patel S, Mayer U, Steinmetz MO, Kammerer RA; , J Biol Chem. 2006;281:28408-28414.: Structure of the extracellular domain of Tie receptor tyrosine kinases and localization of the angiopoietin-binding epitope. PUBMED:16849318 EPMC:16849318

  2. Barton WA, Tzvetkova-Robev D, Miranda EP, Kolev MV, Rajashankar KR, Himanen JP, Nikolov DB; , Nat Struct Mol Biol. 2006;13:524-532.: Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex. PUBMED:16732286 EPMC:16732286


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR018941

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [PUBMED:3291115]:

  • Serine/threonine-protein kinases
  • Tyrosine-protein kinases
  • Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human [PUBMED:12471243]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [PUBMED:12368087]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [PUBMED:15078142], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [PUBMED:15320712].

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups [PUBMED:12471243]:

  • Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis [PUBMED:19275641]. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction [PUBMED:16700535].

  • Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [PUBMED:15845350].

Angiogenesis is a physiological process whereby new blood vessels are formed from existing ones. It is essential for tissue repair and regeneration during wound healing but also plays important roles in many pathological processes including tumor growth and metastasis [PUBMED:16849318, PUBMED:16732286]. Angiogenesis is regulated in part by the receptor protein tyrosine kinase Tie2 and its ligands, the angiopoietins. The angiopoietin-binding site is harbord by the N-terminal two immunoglobulin-like (Ig-like) domains of Tie2 [PUBMED:16849318].

The angiopoietin-1 receptor contains the Tie-2 Ig-like domain. This protein is a tyrosine-kinase transmembrane receptor for angiopoietin 1. It probably regulates endothelial cell proliferation, differentiation and guides the proper patterning of endothelial cells during blood vessel formation.

Tie2 contains not two but three immunoglobulin domains. They fold together with the three epidermal growth factor domains to form a compact, arrowhead-shaped structure [PUBMED:16732286].

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 Ig (CL0011), which has the following description:

Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions. The superfamily can be divided into discrete structural sets, by the presence or absence of beta-strands in the structure and the length of the domains [1]. Proteins containing domains of the C1 and V-sets are mostly molecules of the vertebrate immune system. Proteins of the C2-set are mainly lymphocyte antigens, this differs from the composition of the C2-set as originally proposed [1]. The I-set is intermediate in structure between the C1 and V-sets and is found widely in cell surface proteins as well as intracellular muscle proteins.

The clan contains the following 24 members:

A2M Adeno_E3_CR1 Adhes-Ig_like C1-set C2-set C2-set_2 Herpes_gE Herpes_gI Herpes_glycop_D I-set ICAM_N ig Ig_2 Ig_3 Ig_Tie2_1 IZUMO K1 Lep_receptor_Ig Marek_A PTCRA Receptor_2B4 SVA V-set V-set_CD47

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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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
(4)
Full
(53)
Representative proteomes NCBI
(50)
Meta
(0)
RP15
(1)
RP35
(2)
RP55
(6)
RP75
(19)
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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
(4)
Full
(53)
Representative proteomes NCBI
(50)
Meta
(0)
RP15
(1)
RP35
(2)
RP55
(6)
RP75
(19)
Alignment:
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Order:
Sequence:
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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
(4)
Full
(53)
Representative proteomes NCBI
(50)
Meta
(0)
RP15
(1)
RP35
(2)
RP55
(6)
RP75
(19)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped 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: Ciani B
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 4
Number in full: 53
Average length of the domain: 95.50 aa
Average identity of full alignment: 79 %
Average coverage of the sequence by the domain: 9.53 %

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 25.0 25.0
Trusted cut-off 49.5 48.0
Noise cut-off 23.4 16.3
Model length: 96
Family (HMM) version: 4
Download: download the raw HMM for this family

Species distribution

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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 Ig_Tie2_1 domain has been found. There are 2 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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