Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
30  structures 329  species 5  interactions 2251  sequences 46  architectures

Family: Cullin (PF00888)

Summary: Cullin family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Cullin". More...

Cullin Edit Wikipedia article

Cullin
PDB 1ldk EBI.jpg
structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex
Identifiers
Symbol Cullin
Pfam PF00888
InterPro IPR001373
PROSITE PDOC00967
SCOP 1ldj
SUPERFAMILY 1ldj
Cullin protein neddylation domain
PDB 1ldk EBI.jpg
structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex
Identifiers
Symbol Cullin_Nedd8
Pfam PF10557
InterPro IPR019559

Cullins are a family of hydrophobic proteins providing a scaffold for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form Cullin-RING ubiquitin ligases (CRLs) that are highly diverse and play a role in a myriad of cellular processes.

Human genome contains seven cullin genes:

CUL1, 2, 3, 4A, 4B, 5 and 7 each form part of a multi-subunit ubiquitin complex.

Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms.[1] The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as the APC2 subunit of the anaphase-promoting complex/cyclosome and the p53 cytoplasmic anchor PARC; both APC2 and PARC have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins.[2][3][4]

With the exception of APC2, each member of the cullin family is modified by Nedd8 and several cullins function in Ubiquitin-dependent proteolysis, a process in which the 26S proteasome recognises and subsequently degrades a target protein tagged with K48-linked poly-ubiquitin chains. Nedd8/Rub1 is a small ubiquitin-like protein, which was originally found to be conjugated to Cdc53, a cullin component of the SCF (Skp1-Cdc53/CUL1-F-box protein) E3 Ub ligase complex in Saccharomyces cerevisiae (Baker's yeast), and Nedd8 modification has now emerged as a regulatory pathway of fundamental importance for cell cycle control and for embryogenesis in metazoans. The only identified Nedd8 substrates are cullins. Neddylation results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue.[5]

References[edit]

  1. ^ Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM (June 1996). "cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family". Cell 85 (6): 829–39. doi:10.1016/S0092-8674(00)81267-2. PMID 8681378. 
  2. ^ Petroski MD, Deshaies RJ (January 2005). "Function and regulation of cullin-RING ubiquitin ligases". Nat. Rev. Mol. Cell Biol. 6 (1): 9–20. doi:10.1038/nrm1547. PMID 15688063. 
  3. ^ Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP (April 2002). "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature 416 (6882): 703–9. doi:10.1038/416703a. PMID 11961546. 
  4. ^ Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y, Zheng N (November 2004). "Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases". Cell 119 (4): 517–28. doi:10.1016/j.cell.2004.10.019. PMID 15537541. 
  5. ^ Pan ZQ, Kentsis A, Dias DC, Yamoah K, Wu K (March 2004). "Nedd8 on cullin: building an expressway to protein destruction". Oncogene 23 (11): 1985–97. doi:10.1038/sj.onc.1207414. PMID 15021886. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR001373

This article incorporates text from the public domain Pfam and InterPro IPR019559


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.

Cullin family Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001373

Cullins are a family of hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3). Cullins are found throughout eukaryotes. Humans express seven cullins (Cul1, 2, 3, 4A, 4B, 5 and 7), each forming part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) [PUBMED:8681378], play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as the APC2 subunit of the anaphase-promoting complex/cyclosome and the p53 cytoplasmic anchor PARC; both APC2 and PARC have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins [PUBMED:15688063, PUBMED:11961546, PUBMED:15537541].

This entry represents the N-terminal region of cullin proteins, which consists of several domains, including cullin repeat domain, a 4-helical bundle domain, an alpha+beta domain, and a winged helix-like domain.

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...

Loading domain graphics...

Alignments

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

View options

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

  Seed
(47)
Full
(2251)
Representative proteomes NCBI
(2160)
Meta
(44)
RP15
(530)
RP35
(800)
RP55
(1185)
RP75
(1484)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

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

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

Format an alignment

  Seed
(47)
Full
(2251)
Representative proteomes NCBI
(2160)
Meta
(44)
RP15
(530)
RP35
(800)
RP55
(1185)
RP75
(1484)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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

  Seed
(47)
Full
(2251)
Representative proteomes NCBI
(2160)
Meta
(44)
RP15
(530)
RP35
(800)
RP55
(1185)
RP75
(1484)
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.

Pfam alignments:

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_1149 (release 3.0)
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 47
Number in full: 2251
Average length of the domain: 484.10 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 65.66 %

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 23.0 23.0
Trusted cut-off 23.0 23.2
Noise cut-off 22.8 22.9
Model length: 588
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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...

Loading sunburst data...

Tree controls

Hide

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

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 5 interactions for this family. More...

CPSF_A TIP120 Cullin_Nedd8 zf-C3HC4 HEAT

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 Cullin domain has been found. There are 30 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...