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35  structures 88  species 4  interactions 228  sequences 12  architectures

Family: Cbl_N (PF02262)

Summary: CBL proto-oncogene N-terminal domain 1

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This is the Wikipedia entry entitled "Cbl TKB domain". More...

Cbl TKB domain Edit Wikipedia article

CBL proto-oncogene N-terminal domain 1 (four-helix bundle)
PDB 1b47 EBI.jpg
structure of the n-terminal domain of cbl in complex with its binding site in zap-70
Identifiers
Symbol Cbl_N
Pfam PF02262
InterPro IPR003153
SCOP 1b47
SUPERFAMILY 1b47
CBL proto-oncogene N-terminus, EF hand-like domain
PDB 1b47 EBI.jpg
structure of the n-terminal domain of cbl in complex with its binding site in zap-70
Identifiers
Symbol Cbl_N2
Pfam PF02761
InterPro IPR014741
SCOP 1b47
SUPERFAMILY 1b47
CBL proto-oncogene N-terminus, SH2-like domain
PDB 1b47 EBI.jpg
structure of the n-terminal domain of cbl in complex with its binding site in zap-70
Identifiers
Symbol Cbl_N3
Pfam PF02762
InterPro IPR014742
SCOP 1b47
SUPERFAMILY 1b47

In molecular biology, the Cbl TKB domain (tyrosine kinase binding domain), also known as the phosphotyrosine binding (PTB) domain is a conserved region found at the N-terminus of Cbl adaptor proteins. This N-terminal region is composed of three evolutionarily conserved domains: an N-terminal four-helix bundle domain, an EF hand-like domain and a SH2-like domain, which together are known to bind to phosphorylated tyrosine residues.


References[edit]

This article incorporates text from the public domain Pfam and InterPro IPR014742

This article incorporates text from the public domain Pfam and InterPro IPR014741

This article incorporates text from the public domain Pfam and InterPro IPR003153

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.

CBL proto-oncogene N-terminal domain 1 Provide feedback

Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. Cbl_N is comprised of 3 structural domains of which this is the first - a four helix bundle.

Literature references

  1. Meng W, Sawasdikosol S, Burakoff SJ, Eck MJ; , Nature 1999;398:84-90.: Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase PUBMED:10078535 EPMC:10078535


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003153

Cbl (Casitas B-lineage lymphoma) is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface.

The N-terminal region of Cbl contains a Cbl-type phosphotyrosine-binding (Cbl-PTB) domain, which is composed of three evolutionarily conserved domains: an N-terminal four-helix bundle (4H) domain, an EF hand-like calcium-binding domain, and a divergent SH2-like domain. The calcium-bound EF-hand wedges between the 4H and SH2 domains, and roughly determines their relative orientation. The Cbl-PTB domain has also been named Cbl N-terminal (Cbl-N) or tyrosine kinase binding (TKB) domain [PUBMED:10078535, PUBMED:18840649].

The N-terminal 4H domain contains four long alpha-helices. The C and D helices in this domain pack against the adjacent EF-hand-like domain, and a highly conserved loop connecting the A and B helices contacts the SH2-like domain. The EF-hand motif is similar to classical EF-hand proteins. The SH2-like domain retains the general helix-sheet-helix architecture of the SH2 fold, but lacks the secondary beta-sheet, comprising beta-strands D', E and F, and also a prominent BG loop [PUBMED:10078535].

This entry represents the N-terminal four-helical bundle domain.

Gene Ontology

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Domain organisation

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

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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.

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Full
(228)
Representative proteomes NCBI
(222)
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(24)
RP35
(34)
RP55
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RP75
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  Seed
(3)
Full
(228)
Representative proteomes NCBI
(222)
Meta
(0)
RP15
(24)
RP35
(34)
RP55
(66)
RP75
(117)
Alignment:
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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
(3)
Full
(228)
Representative proteomes NCBI
(222)
Meta
(0)
RP15
(24)
RP35
(34)
RP55
(66)
RP75
(117)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
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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: Pfam-B_3949 (release 5.2)
Previous IDs: none
Type: Domain
Author: Bateman A, Mian N, Griffiths-Jones SR
Number in seed: 3
Number in full: 228
Average length of the domain: 122.10 aa
Average identity of full alignment: 60 %
Average coverage of the sequence by the domain: 17.48 %

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 25.1 25.8
Noise cut-off 20.1 24.4
Model length: 130
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

Cbl_N2 Cbl_N Cbl_N3 zf-C3HC4

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 Cbl_N domain has been found. There are 35 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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