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.
3  structures 1024  species 3  interactions 1274  sequences 39  architectures

Family: CAS_CSE1 (PF03378)

Summary: CAS/CSE protein, C-terminus

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 "CAS/CSE protein family". More...

CAS/CSE protein family Edit Wikipedia article

CAS/CSE protein, C-terminus
PDB 1z3h EBI.jpg
the exportin cse1 in its cargo-free, cytoplasmic state
Identifiers
Symbol CAS_CSE1
Pfam PF03378
InterPro IPR005043
Cse1
PDB 1z3h EBI.jpg
the exportin cse1 in its cargo-free, cytoplasmic state
Identifiers
Symbol Cse1
Pfam PF08506
Pfam clan CL0020
InterPro IPR013713

In molecular biology, the CAS/CSE protein family is a family of proteins which includes mammalian cellular apoptosis susceptibility (CAS) proteins and yeast chromosome-segregation protein, CSE1.[1] CAS is involved in both cellular apoptosis and proliferation.[2][3] Apoptosis is inhibited in CAS-depleted cells, while the expression of CAS correlates to the degree of cellular proliferation. Like CSE1, it is essential for the mitotic checkpoint in the cell cycle (CAS depletion blocks the cell in the G2 phase), and has been shown to be associated with the microtubule network and the mitotic spindle,[3] as is the protein MEK, which is thought to regulate the intracellular localization (predominantly nuclear vs. predominantly cytosolic) of CAS. In the nucleus, CAS acts as a nuclear transport factor in the importin pathway.[4] The importin pathway mediates the nuclear transport of several proteins that are necessary for mitosis and further progression. CAS is therefore thought to affect the cell cycle through its effect on the nuclear transport of these proteins.[5] Since apoptosis also requires the nuclear import of several proteins (such as P53 and transcription factors), it has been suggested that CAS also enables apoptosis by facilitating the nuclear import of at least a subset of these essential proteins.[6]

The CAS/CSE family of proteins consist of two domains. An N-terminal Cse1 domain, which contains HEAT repeats, and a C-terminal domain.[7]

References

  1. ^ Brinkmann U, Brinkmann E, Gallo M, Pastan I (October 1995). "Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10427–31. doi:10.1073/pnas.92.22.10427. PMC 40810Freely accessible. PMID 7479798. 
  2. ^ Brinkmann U, Brinkmann E, Gallo M, Scherf U, Pastan I (May 1996). "Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis". Biochemistry. 35 (21): 6891–9. doi:10.1021/bi952829+. PMID 8639641. 
  3. ^ a b Scherf U, Pastan I, Willingham MC, Brinkmann U (April 1996). "The human CAS protein which is homologous to the CSE1 yeast chromosome segregation gene product is associated with microtubules and mitotic spindle". Proc. Natl. Acad. Sci. U.S.A. 93 (7): 2670–4. doi:10.1073/pnas.93.7.2670. PMC 39688Freely accessible. PMID 8610099. 
  4. ^ Kutay U, Bischoff FR, Kostka S, Kraft R, Gorlich D (September 1997). "Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor". Cell. 90 (6): 1061–71. doi:10.1016/S0092-8674(00)80372-4. PMID 9323134. 
  5. ^ Kutay U, Bischoff FR, Kostka S, Kraft R, Görlich D (September 1997). "Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor". Cell. 90 (6): 1061–71. doi:10.1016/S0092-8674(00)80372-4. PMID 9323134. 
  6. ^ Brinkmann U (March 1998). "CAS, the human homologue of the yeast chromosome-segregation gene CSE1, in proliferation, apoptosis, and cancer". Am. J. Hum. Genet. 62 (3): 509–13. doi:10.1086/301773. PMC 1376967Freely accessible. PMID 9497270. 
  7. ^ Cook, A.; Fernandez, E.; Lindner, D.; Ebert, J.; Schlenstedt, G.; Conti, E. (2005). "The Structure of the Nuclear Export Receptor Cse1 in Its Cytosolic State Reveals a Closed Conformation Incompatible with Cargo Binding". Molecular Cell. 18 (3): 355–367. doi:10.1016/j.molcel.2005.03.021. PMID 15866177. 

This article incorporates text from the public domain Pfam and InterPro IPR005043

This article incorporates text from the public domain Pfam and InterPro IPR013713

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.

CAS/CSE protein, C-terminus Provide feedback

Mammalian cellular apoptosis susceptibility (CAS) proteins are homologous to the yeast chromosome-segregation protein, CSE1 [1]. This family aligns the C-terminal halves (approximately). CAS is involved in both cellular apoptosis and proliferation [2,3]. Apoptosis is inhibited in CAS-depleted cells, while the expression of CAS correlates to the degree of cellular proliferation. Like CSE1, it is essential for the mitotic checkpoint in the cell cycle (CAS depletion blocks the cell in the G2 phase), and has been shown to be associated with the microtubule network and the mitotic spindle [3] as is the protein MEK, which is thought to regulate the intracellular localisation (predominantly nuclear vs. predominantly cytosolic) of CAS. In the nucleus, CAS acts as a nuclear transport factor in the importin pathway [4]. The importin pathway mediates the nuclear transport of several proteins that are necessary for mitosis and further progression. CAS is therefore thought to affect the cell cycle through its effect on the nuclear transport of these proteins [4]. Since apoptosis also requires the nuclear import of several proteins (such as P53 and transcription factors), it has been suggested that CAS also enables apoptosis by facilitating the nuclear import of at least a subset of these essential proteins [5].

Literature references

  1. Brinkmann U, Brinkmann E, Gallo M, Pastan I; , Proc Natl Acad Sci U S A 1995;92:10427-10431.: Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1. PUBMED:7479798 EPMC:7479798

  2. Brinkmann U, Brinkmann E, Gallo M, Scherf U, Pastan I; , Biochemistry 1996;35:6891-6899.: Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis. PUBMED:8639641 EPMC:8639641

  3. Scherf U, Pastan I, Willingham MC, Brinkmann U; , Proc Natl Acad Sci U S A 1996;93:2670-2674.: The human CAS protein which is homologous to the CSE1 yeast chromosome segregation gene product is associated with microtubules and mitotic spindle. PUBMED:8610099 EPMC:8610099

  4. Kutay U, Bischoff FR, Kostka S, Kraft R, Gorlich D; , Cell 1997;90:1061-1071.: Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor. PUBMED:9323134 EPMC:9323134

  5. Brinkmann U; , Am J Hum Genet 1998;62:509-513.: CAS, the human homologue of the yeast chromosome-segregation gene CSE1, in proliferation, apoptosis, and cancer. PUBMED:9497270 EPMC:9497270


This tab holds annotation information from the InterPro database.

InterPro entry IPR005043

Mammalian cellular apoptosis susceptibility (CAS) proteins and the yeast chromosome-segregation protein, CSE1 are homologous [PUBMED:7479798]. CAS is involved in both cellular apoptosis and proliferation [PUBMED:8639641, PUBMED:8610099]. Apoptosis is inhibited in CAS-depleted cells, while the expression of CAS correlates to the degree of cellular proliferation. Like CSE1, it is essential for the mitotic checkpoint in the cell cycle (CAS depletion blocks the cell in the G2 phase), and has been shown to be associated with the microtubule network and the mitotic spindle [PUBMED:8610099], as is the protein MEK, which is thought to regulate the intracellular localization (predominantly nuclear vs. predominantly cytosolic) of CAS. In the nucleus, CAS acts as a nuclear transport factor in the importin pathway [PUBMED:9323134]. The importin pathway mediates the nuclear transport of several proteins that are necessary for mitosis and further progression. CAS is therefore thought to affect the cell cycle through its effect on the nuclear transport of these proteins [PUBMED:9323134]. Since apoptosis also requires the nuclear import of several proteins (such as P53 and transcription factors), it has been suggested that CAS also enables apoptosis by facilitating the nuclear import of at least a subset of these essential proteins [PUBMED:9497270]. This entry represents the C-terminal portion of these proteins. Structural studies of the yeast CSE1 protein indicate that this domain binds to both the transport-orchestrating protein RanGTP and the cargo molecule that is being exported [PUBMED:15602554].

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...

Pfam Clan

This family is a member of clan TPR (CL0020), which has the following description:

Tetratricopeptide-like repeats are found in a numerous and diverse proteins involved in such functions as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The clan contains the following 149 members:

Adaptin_N Alkyl_sulf_dimr ANAPC3 ANAPC5 ANAPC8 API5 Arm Arm_2 Arm_3 Atx10homo_assoc B56 BAF250_C BTAD CAS_CSE1 ChAPs CHIP_TPR_N CLASP_N Clathrin Clathrin-link Clathrin_H_link Clathrin_propel Cnd1 Cnd3 Coatomer_E Cohesin_HEAT Cohesin_load ComR_TPR COPI_C CPL CRM1_C Cse1 DHR-2 DNA_alkylation Drf_FH3 Drf_GBD DUF1822 DUF2019 DUF2225 DUF3385 DUF3458_C DUF3808 DUF3856 DUF4042 DUF924 EST1 EST1_DNA_bind FAT Fis1_TPR_C Fis1_TPR_N Foie-gras_1 GUN4_N HAT HEAT HEAT_2 HEAT_EZ HEAT_PBS HemY_N HrpB1_HrpK IBB IBN_N IFRD KAP Leuk-A4-hydro_C LRV LRV_FeS MA3 MIF4G MIF4G_like MIF4G_like_2 MMS19_C Mo25 MRP-S27 NARP1 Neurochondrin Nipped-B_C Nro1 NSF Paf67 ParcG PC_rep PHAT PI3Ka PknG_TPR PPP5 PPR PPR_1 PPR_2 PPR_3 PPR_long PPTA Proteasom_PSMB PUF Rab5-bind Rapsyn_N RIX1 RPM2 RPN7 Sel1 SHNi-TPR SNAP SPO22 SRP_TPR_like ST7 Suf SusD-like SusD-like_2 SusD-like_3 SusD_RagB SYCP2_ARLD TAF6_C TAL_effector TAtT Tcf25 TIP120 TOM20_plant TPR_1 TPR_10 TPR_11 TPR_12 TPR_14 TPR_15 TPR_16 TPR_17 TPR_18 TPR_19 TPR_2 TPR_20 TPR_21 TPR_3 TPR_4 TPR_5 TPR_6 TPR_7 TPR_8 TPR_9 TPR_MalT UNC45-central Upf2 V-ATPase_H_C V-ATPase_H_N Vac14_Fab1_bd Vitellogenin_N Vps39_1 W2 Wzy_C_2 Xpo1 YcaO_C YfiO Zmiz1_N

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, the UniProtKB sequence database, 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
(15)
Full
(1274)
Representative proteomes UniProt
(1830)
NCBI
(2045)
Meta
(9)
RP15
(386)
RP35
(731)
RP55
(1016)
RP75
(1222)
Jalview View  View  View  View  View  View  View  View  View 
HTML View  View               
PP/heatmap 1 View               

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

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

Format an alignment

  Seed
(15)
Full
(1274)
Representative proteomes UniProt
(1830)
NCBI
(2045)
Meta
(9)
RP15
(386)
RP35
(731)
RP55
(1016)
RP75
(1222)
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
(15)
Full
(1274)
Representative proteomes UniProt
(1830)
NCBI
(2045)
Meta
(9)
RP15
(386)
RP35
(731)
RP55
(1016)
RP75
(1222)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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_3786 (release 6.6)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Mifsud W
Number in seed: 15
Number in full: 1274
Average length of the domain: 387.30 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 43.71 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.8 21.8
Trusted cut-off 21.8 21.9
Noise cut-off 21.3 21.7
Model length: 443
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

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 3 interactions for this family. More...

IBN_N Ras Cse1

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 CAS_CSE1 domain has been found. There are 3 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.

Loading structure mapping...