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3  structures 1469  species 0  interactions 2030  sequences 47  architectures

Family: CAS_CSE1 (PF03378)

Summary: CAS/CSE protein, C-terminus

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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

  6. Cook A, Fernandez E, Lindner D, Ebert J, Schlenstedt G, Conti E; , Mol Cell 2005;18:355-367.: The structure of the nuclear export receptor Cse1 in its cytosolic state reveals a closed conformation incompatible with cargo binding. PUBMED:15866177 EPMC:15866177


This tab holds annotation information from the InterPro database.

InterPro entry IPR005043

This entry represents the C-terminal domain of XPO2. Structural studies of its yeast homologue, Cse1, indicate that this domain binds to both the transport-orchestrating protein RanGTP and the cargo molecule that is being exported [ PUBMED:15602554 ].

Exportin-2, also known as CAS, is an export receptor for importin-alpha [ PUBMED:9323134 ]. It binds strongly to importin alpha only in the presence of RanGTP, forming an importin alpha/CAS/RanGTP complex. Exportin-2 mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates have been released into the nucleoplasm [ PUBMED:10394916 ].

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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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 252 members:

14-3-3 AAR2 Aconitase_B_N Adaptin_N Alkyl_sulf_dimr ANAPC3 ANAPC5 ANAPC8 Apc1_MidN APC_rep API5 Aquarius_N Arm Arm_2 Arm_3 Arm_vescicular Atx10homo_assoc B56 BAF250_C BRO1 BTAD CAS_CSE1 ChAPs CHIP_TPR_N CID CLASP_N Clathrin Clathrin-link Clathrin_H_link Clathrin_propel Cnd1 Cnd1_N Cnd3 CNOT1_CAF1_bind CNOT1_HEAT_N CNOT1_TTP_bind Coatomer_E Cohesin_HEAT Cohesin_load ComR_TPR COPI_C CPL CRM1_C CRM1_repeat CRM1_repeat_3 Cse1 CTK3 CTNNBL Cullin DHR-2_Lobe_A DHR-2_Lobe_C DIL DNA-PKcs_N DNA_alkylation DNAPKcs_CC1-2 DNAPKcs_CC3 DNAPKcs_CC5 Dopey_N Drf_FH3 Drf_GBD DUF1822 DUF2019 DUF2225 DUF3385 DUF3458_C DUF3730 DUF3856 DUF4042 DUF4704 DUF5071 DUF5106 DUF5588 DUF5691 DUF6340 DUF6377 DUF6584 DUF924 E_motif EAD11 eIF-3c_N ELMO_ARM EST1 EST1_DNA_bind FA_FANCE FANCF FANCI_HD1 FANCI_HD2 FANCI_S1 FANCI_S1-cap FANCI_S2 FANCI_S3 FANCI_S4 FAT Fes1 Fis1_TPR_C Fis1_TPR_N Focadhesin Foie-gras_1 GET4 GLE1 GUN4_N HAT HEAT HEAT_2 HEAT_EZ HEAT_PBS HEAT_UF HemY_N HMW1C_N HPS6_C HrpB1_HrpK HSM3_C HSM3_N Hyccin IBB IBN_N IFRD Iml2-TPR_39 Importin_rep Importin_rep_2 Importin_rep_3 Importin_rep_4 Importin_rep_5 Importin_rep_6 Insc_C Ints3_N KAP Kinetochor_Ybp2 Laa1_Sip1_HTR5 Leuk-A4-hydro_C LRV LRV_FeS MA3 Mad3_BUB1_I MAP3K_TRAF_bd MIF4G MIF4G_like MIF4G_like_2 MIX MMS19_C Mo25 MRP-S27 Mtf2 MUN NatA_aux_su Neurobeachin Neurochondrin Nic96 Nipped-B_C Not1 Nro1 NSF Paf67 ParcG PAT1 PC_rep PDS5 Peptidase_M9_N PHAT PI3Ka PknG_TPR PPP5 PPR PPR_1 PPR_2 PPR_3 PPR_long PPTA Proteasom_PSMB PUF PUL RAI16-like Rapsyn_N Rcd1 RIH_assoc RINT1_TIP1 RIX1 RNPP_C RPM2 RPN6_N RPN7 RYDR_ITPR Sel1 SHNi-TPR SIL1 SLT_L SNAP SPO22 SRP_TPR_like ST7 STAG Suf SusD-like SusD-like_2 SusD-like_3 SusD_RagB SYCP2_ARLD SYMPK_PTA1_N TAF1_subA TAF6_C TAL_effector TAP42 TAtT Tcf25 TIP120 TOM20_plant TPR-S 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_22 TPR_3 TPR_4 TPR_5 TPR_6 TPR_7 TPR_8 TPR_9 TPR_MalT Tra1_ring TRF TTC7_N Type_III_YscG UNC45-central Upf2 Uso1_p115_head V-ATPase_H_C V-ATPase_H_N Vac14_Fab1_bd Vitellogenin_N Vps16_C Vps35 Vps39_1 VPS53_C W2 Wap1 WSLR Wzy_C_2 Xpo1 YcaO_C YfiO Zmiz1_N

Alignments

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  Seed
(15)
Full
(2030)
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(435)
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(941)
RP55
(1566)
RP75
(2067)
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  Seed
(15)
Full
(2030)
Representative proteomes UniProt
(3327)
RP15
(435)
RP35
(941)
RP55
(1566)
RP75
(2067)
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  Seed
(15)
Full
(2030)
Representative proteomes UniProt
(3327)
RP15
(435)
RP35
(941)
RP55
(1566)
RP75
(2067)
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Trees

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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: Repeat
Sequence Ontology: SO:0001068
Author: Mifsud W
Number in seed: 15
Number in full: 2030
Average length of the domain: 390.50 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 44.38 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.0 25.0
Noise cut-off 24.9 24.9
Model length: 443
Family (HMM) version: 18
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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 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.

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