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71  structures 1465  species 0  interactions 12262  sequences 242  architectures

Family: Cullin (PF00888)

Summary: Cullin family

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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
SymbolCullin
PfamPF00888
InterProIPR001373
PROSITEPDOC00967
SCOPe1ldj / SUPFAM
Cullin protein neddylation domain
PDB 1ldk EBI.jpg
structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex
Identifiers
SymbolCullin_Nedd8
PfamPF10557
InterProIPR019559

Cullins are a family of hydrophobic scaffold proteins which provide support 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 myriad cellular processes, most notably protein degradation by ubiquitination.[1][2]

The human genome contains eight cullin genes

There is also a more distant member called ANAPC2 (or APC2), part of the Anaphase-promoting complex.

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

Cullin-RING ubiquitin ligases

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.[3] 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 CUL9, also known as p53 cytoplasmic anchor PARC, and the ANAPC2 subunit of the anaphase-promoting complex/cyclosome; both CUL9 and ANAPC2 have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins.[4][5][6]

Modification by NEDD8

With the exception of ANAPC2, 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.[7]

References

  1. ^ [1]
  2. ^ Bruce, Alberts (2014-11-18). Molecular biology of the cell (Sixth ed.). New York, NY. ISBN 9780815344322. OCLC 887605755.
  3. ^ 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.
  4. ^ Petroski MD, Deshaies RJ (January 2005). "Function and regulation of cullin-RING ubiquitin ligases" (PDF). Nat. Rev. Mol. Cell Biol. 6 (1): 9–20. doi:10.1038/nrm1547. PMID 15688063.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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

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

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Internal database links

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...

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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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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
(344)
Full
(12262)
Representative proteomes UniProt
(21638)
RP15
(2410)
RP35
(5786)
RP55
(10068)
RP75
(13044)
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PP/heatmap 1            

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

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

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  Seed
(344)
Full
(12262)
Representative proteomes UniProt
(21638)
RP15
(2410)
RP35
(5786)
RP55
(10068)
RP75
(13044)
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
(344)
Full
(12262)
Representative proteomes UniProt
(21638)
RP15
(2410)
RP35
(5786)
RP55
(10068)
RP75
(13044)
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.

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
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 344
Number in full: 12262
Average length of the domain: 466.90 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 64.95 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 33.2 33.2
Trusted cut-off 33.2 33.2
Noise cut-off 33.1 33.0
Model length: 619
Family (HMM) version: 24
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 Cullin domain has been found. There are 71 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2K761 View 3D Structure Click here
A0A0G2K959 View 3D Structure Click here
A0A0P0V765 View 3D Structure Click here
A0A0P0WIW4 View 3D Structure Click here
A0A0P0Y8F5 View 3D Structure Click here
A0A0R0G189 View 3D Structure Click here
A0A0R0GND9 View 3D Structure Click here
A0A0R0GND9 View 3D Structure Click here
A0A0R0GS02 View 3D Structure Click here
A0A0R4ISV4 View 3D Structure Click here
A0A1D6FUG6 View 3D Structure Click here
A0A1D6GG24 View 3D Structure Click here
A0A1D6GJM0 View 3D Structure Click here
A0A1D6GVA1 View 3D Structure Click here
A0A1D6H9E6 View 3D Structure Click here
A0A1D6HBQ0 View 3D Structure Click here
A0A1D6HKC3 View 3D Structure Click here
A0A1D6J2B8 View 3D Structure Click here
A0A1D6L6V2 View 3D Structure Click here
A0A1D6MU46 View 3D Structure Click here
A0A1D6N233 View 3D Structure Click here
A0A1D6PVQ2 View 3D Structure Click here
A0A1D8PDR1 View 3D Structure Click here
A0A1D8PRP1 View 3D Structure Click here
A0A286Y8D7 View 3D Structure Click here
A0A2R8QBE5 View 3D Structure Click here
A2A432 View 3D Structure Click here
A3AXY3 View 3D Structure Click here
A4HX19 View 3D Structure Click here
A4I137 View 3D Structure Click here
A4I1H2 View 3D Structure Click here
A4I3U0 View 3D Structure Click here
A4I3U1 View 3D Structure Click here
A4IBR4 View 3D Structure Click here
A4ID94 View 3D Structure Click here
B1WBY1 View 3D Structure Click here
B2RYJ1 View 3D Structure Click here
B2RYJ3 View 3D Structure Click here
B3DIU1 View 3D Structure Click here
B5DF89 View 3D Structure Click here
C6KTD3 View 3D Structure Click here
C6KTD3 View 3D Structure Click here
D3ZEF4 View 3D Structure Click here
D3ZK73 View 3D Structure Click here
D3ZZP8 View 3D Structure Click here
E7FE00 View 3D Structure Click here
F1Q7M5 View 3D Structure Click here
F1QFY1 View 3D Structure Click here
F1REN0 View 3D Structure Click here
F6NVK8 View 3D Structure Click here
F8W428 View 3D Structure Click here
I1JE36 View 3D Structure Click here
I1K3E9 View 3D Structure Click here
I1KN10 View 3D Structure Click here
I1KXS9 View 3D Structure Click here
I1L117 View 3D Structure Click here
I1LMG8 View 3D Structure Click here
I1LWJ8 View 3D Structure Click here
I1MF26 View 3D Structure Click here
I1MRG8 View 3D Structure Click here
I1MZB3 View 3D Structure Click here
I1N157 View 3D Structure Click here
I1N643 View 3D Structure Click here
I1NB34 View 3D Structure Click here
K7KG94 View 3D Structure Click here
K7L5S0 View 3D Structure Click here
K7M138 View 3D Structure Click here
K7MDU0 View 3D Structure Click here
K7TQJ3 View 3D Structure Click here
O13790 View 3D Structure Click here
O14122 View 3D Structure Click here
O60999 View 3D Structure Click here
P0CH31 View 3D Structure Click here
P0CH31 View 3D Structure Click here
P34514 View 3D Structure Click here
P53202 View 3D Structure Click here
Q09760 View 3D Structure Click here
Q0DMY2 View 3D Structure Click here
Q0JC96 View 3D Structure Click here
Q12018 View 3D Structure Click here
Q12440 View 3D Structure Click here
Q13616 View 3D Structure Click here
Q13617 View 3D Structure Click here
Q13618 View 3D Structure Click here
Q13619 View 3D Structure Click here
Q13620 View 3D Structure Click here
Q14999 View 3D Structure Click here
Q17389 View 3D Structure Click here
Q17390 View 3D Structure Click here
Q17391 View 3D Structure Click here
Q17392 View 3D Structure Click here
Q21346 View 3D Structure Click here
Q23639 View 3D Structure Click here
Q24311 View 3D Structure Click here
Q3TCH7 View 3D Structure Click here
Q4CRP5 View 3D Structure Click here
Q4CTM0 View 3D Structure Click here
Q4CUC0 View 3D Structure Click here
Q4CX33 View 3D Structure Click here
Q4CZ35 View 3D Structure Click here
Q4D018 View 3D Structure Click here
Q4D5L7 View 3D Structure Click here
Q4DB05 View 3D Structure Click here
Q4DGF2 View 3D Structure Click here
Q4DVD1 View 3D Structure Click here
Q4DVD1 View 3D Structure Click here
Q4DZU8 View 3D Structure Click here
Q4E4Q7 View 3D Structure Click here
Q54CS2 View 3D Structure Click here
Q54NZ5 View 3D Structure Click here
Q54XF7 View 3D Structure Click here
Q551S9 View 3D Structure Click here
Q5ADM0 View 3D Structure Click here
Q5AJB7 View 3D Structure Click here
Q5BI50 View 3D Structure Click here
Q5JMQ6 View 3D Structure Click here
Q5XI53 View 3D Structure Click here
Q5ZC88 View 3D Structure Click here
Q6NYS3 View 3D Structure Click here
Q6YWY5 View 3D Structure Click here
Q6YYL1 View 3D Structure Click here
Q7T2C1 View 3D Structure Click here
Q7XJX7 View 3D Structure Click here
Q86Y37 View 3D Structure Click here
Q874R3 View 3D Structure Click here
Q8BZQ7 View 3D Structure Click here
Q8H1U5 View 3D Structure Click here
Q8IAU5 View 3D Structure Click here
Q8IP45 View 3D Structure Click here
Q8IWT3 View 3D Structure Click here
Q8LGH4 View 3D Structure Click here
Q8R0X2 View 3D Structure Click here
Q8VE73 View 3D Structure Click here
Q93034 View 3D Structure Click here
Q93VL5 View 3D Structure Click here
Q94AH6 View 3D Structure Click here
Q9C9L0 View 3D Structure Click here
Q9D4H8 View 3D Structure Click here
Q9D5V5 View 3D Structure Click here
Q9JJ31 View 3D Structure Click here
Q9JLV5 View 3D Structure Click here
Q9SRZ0 View 3D Structure Click here
Q9STG3 View 3D Structure Click here
Q9SZ75 View 3D Structure Click here
Q9UJX6 View 3D Structure Click here
Q9V9R2 View 3D Structure Click here
Q9VAQ0 View 3D Structure Click here
Q9VU33 View 3D Structure Click here
Q9VU33 View 3D Structure Click here
Q9W1E5 View 3D Structure Click here
Q9WTX6 View 3D Structure Click here
Q9XIE8 View 3D Structure Click here
Q9XIE9 View 3D Structure Click here
Q9XZJ3 View 3D Structure Click here
Q9ZVH4 View 3D Structure Click here