| General information | | DisProt: | DP00742 | | Name: | Smoothelin-like protein 1 | | Synonym(s): | SMTL1_MOUSE
Calponin homology-associated smooth muscle protein
CHASM
SMTNL1
| | First appeared in release: | Release 6.01 (10/15/2012) | | UniProt: | Q99LM3 | | UniGene: | Mm.33452 | | SwissProt: | SMTL1_MOUSE | | TrEMBL: | | | NCBI (GI): | 13195656 | | Source organism: | Mus musculus (Mouse) | | Sequence length: | 459 | | Percent disordered: | 78% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
| | | | | |
MEQTEGNSSE DGTTVSPTAG NLETPGSQGI AEEVAEGTVG TSDKEGPSDW AEHLCKAASK - 60
SGESGGSPGE ASILDELKTD LQGEARGKDE AQGDLAEEKV GKEDTTAASQ EDTGKKEETK - 120
PEPNEVREKE EAMLASEKQK VDEKETNLES KEKSDVNDKA KPEPKEDAGA EVTVNEAETE - 180
SQEEADVKDQ AKPELPEVDG KETGSDTKEL VEPESPTEEQ EQGKENESEE RAAVIPSSPE - 240
EWPESPTDEG PSLSPDGLAP ESTGETSPSA SESSPSEVPG SPTEPQPSEK KKDRAPERRV - 300
SAPSRPRGPR AQNRKAIMDK FGGAASGPTA LFRNTKAAGA AIGGVKNMLL EWCRAMTRNY - 360
EHVDIQNFSS SWSSGMAFCA LIHKFFPEAF DYAELDPAKR RHNFTLAFST AEKLADCAQL - 420
LEVDDMVRLA VPDSKCVYTY IQELYRSLVQ KGLVKTKKK
|
| Functional narrative |
Plays a role in the regulation of contractile properties of both striated and smooth muscles. When unphosphorylated, may inhibit myosin dephosphorylation. Phosphorylation at Ser-301 reduces this inhibitory activity.
------------------------------------------------------------------------------------------------------------------
Copyright The UniProt Consortium, http://www.uniprot.org/terms.
Distributed under the Creative Commons Attribution-NoDerivs License.
------------------------------------------------------------------------------------------------------------------
1) The IQ domain found within ordered calponin homology (CH) domain facilitates apo-calmodulin binding;
2) The intrinsically disordered region (IDR) proximal to the CH-domain and the CH domain are required for tropomyosin binding. (JK MacDonald)
|
| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
|
| Region 1 | | Type: | Disordered | | Name: | N-terminal domain | | Location: | 1 - 346 | | Length: | 346 | | Region sequence: |
MEQTEGNSSEDGTTVSPTAGNLETPGSQGIAEEVAEGTVGTSDKEGPSDWAEHLCKAASK
SGESGGSPGEASILDELKTDLQGEARGKDEAQGDLAEEKVGKEDTTAASQEDTGKKEETK
PEPNEVREKEEAMLASEKQKVDEKETNLESKEKSDVNDKAKPEPKEDAGAEVTVNEAETE
SQEEADVKDQAKPELPEVDGKETGSDTKELVEPESPTEEQEQGKENESEERAAVIPSSPE
EWPESPTDEGPSLSPDGLAPESTGETSPSASESSPSEVPGSPTEPQPSEKKKDRAPERRV
SAPSRPRGPRAQNRKAIMDKFGGAASGPTALFRNTKAAGAAIGGVK | | Modification type: | | | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | | Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV
- Nuclear magnetic resonance (NMR)
| References:
- MacDonald JA, Ishida H, Butler EI, Ulke-Lemée A, Chappellaz M, Tulk SE, Chik JK, Vogel HJ. "Intrinsically disordered N-terminus of calponin homology-associated smooth muscle protein (CHASM) interacts with the calponin homology domain to enable tropomyosin binding." Biochemistry. 2012; 51(13): 2694-705. PubMed: 22424482
- Wooldridge AA, Fortner CN, Lontay B, Akimoto T, Neppl RL, Facemire C, Datto MB, Kwon A, McCook E, Li P, Wang S, Thresher RJ, Miller SE, Perriard JC, Gavin TP, Hickner RC, Coffman TM, Somlyo AV, Yan Z, Haystead TA. "Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle." J. Biol. Chem.. 2008; 283(17): 11850-9. PubMed: 18310078
| Comments:According to Wooldridge et al (2008), "Preliminary CD analysis and NMR studies with N-terminal domain indicate the structure is disordered, (T. Haystead, unpublished observations)." MacDonald et al (2012) found predictive supporting evidence for N-terminal disorder.
|
| Region 2 | | Type: | Disordered w/ Residual Structure | | Name: | CHASM-pxIDR (IDR proximal to CH-domain) | | Location: | 195 - 345 | | Length: | 151 | | Region sequence: |
LPEVDGKETGSDTKELVEPESPTEEQEQGKENESEERAAVIPSSPEEWPESPTDEGPSLS
PDGLAPESTGETSPSASESSPSEVPGSPTEPQPSEKKKDRAPERRVSAPSRPRGPRAQNR
KAIMDKFGGAASGPTALFRNTKAAGAAIGGV | | Modification type: | Complex
Fragment
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Modification site
Molecular recognition effectors
Molecular assembly
| | Functional subclasses: | Intraprotein interaction
Phosphorylation
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (293 K; pH: 6.8; Bis-Tris (buffer) 20 mM; CHASM-CH fragment (K346-K459) 0.3 mM; CHASM-pxIDR fragment (L195-V345); DSS 0.5 mM; DTT 5 mM; KCl 50 mM)
- Circular dichroism (CD) spectroscopy, far-UV (295 K; pH: 7; CHASM-CH fragment (K346-K459) (alone or with pxIDR) 5 uM; CHASM-pxIDR fragment (L195-V345) (alone or with CH domain) 5 uM; potassium phosphate (buffer) 20 mM)
| References:
- MacDonald JA, Ishida H, Butler EI, Ulke-Lemée A, Chappellaz M, Tulk SE, Chik JK, Vogel HJ. "Intrinsically disordered N-terminus of calponin homology-associated smooth muscle protein (CHASM) interacts with the calponin homology domain to enable tropomyosin binding." Biochemistry. 2012; 51(13): 2694-705. PubMed: 22424482
| Comments:Phosporylation site at S301.
MacDonald et al (2012) describe "potential structure within the pxIDR that could provide an intramolecular interface between the globular CH domain and intrinsically disordered N-terminal region."
Author JK MacDonald adds,
1) The IQ domain found within the ordered calponin homology (CH) domain facilitates apo-calmodulin binding.
2) The IDR proximal to CH-domain and the CH domain are required for tropomyosin binding.
|
| Region 3 | | Type: | Ordered | | Name: | CH domain | | Location: | 346 - 448 | | Length: | 103 | | Region sequence: |
KNMLLEWCRAMTRNYEHVDIQNFSSSWSSGMAFCALIHKFFPEAFDYAELDPAKRRHNFT
LAFSTAEKLADCAQLLEVDDMVRLAVPDSKCVYTYIQELYRSL | | Modification type: | Fragment
| | PDB: | 2JV9:A | | Structural/functional type: | Function arises from the ordered state
| | Functional classes: | Molecular recognition effectors
Molecular assembly
| | Functional subclasses: | Intraprotein interaction
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (293 K; pH: 7; 90% H2O/10% D2O (or 100% D2O); DSS 0.5 mM; SMTNL1-CH fragment (K346-K459) (PDB 2JV9. (0.5-1.0 mM)) 1 mM; sodium azide (0.03%); sodium phosphate 1 mM; [U-2H] DTT 10 mM)
- Circular dichroism (CD) spectroscopy, far-UV (295 K; pH: 7; CHASM-CH fragment (K346-K459) (alone or with pxIDR) 5 uM; CHASM-pxIDR fragment (L195-V345) (alone or with CH domain) 5 uM; potassium phosphate (buffer) 20 mM)
- Nuclear magnetic resonance (NMR) (293 K; pH: 6.8; Bis-Tris (buffer) 20 mM; CHASM-CH fragment (K346-K459) 0.3 mM; CHASM-pxIDR fragment (L195-V345); DSS 0.5 mM; DTT 5 mM; KCl 50 mM)
| References:
- Ishida H, Borman MA, Ostrander J, Vogel HJ, MacDonald JA. "Solution structure of the calponin homology (CH) domain from the smoothelin-like 1 protein: a unique apocalmodulin-binding mode and the possible role of the C-terminal type-2 CH-domain in smooth muscle relaxation." J. Biol. Chem.. 2008; 283(29): 20569-78. PubMed: 18477568
- MacDonald JA, Ishida H, Butler EI, Ulke-Lemée A, Chappellaz M, Tulk SE, Chik JK, Vogel HJ. "Intrinsically disordered N-terminus of calponin homology-associated smooth muscle protein (CHASM) interacts with the calponin homology domain to enable tropomyosin binding." Biochemistry. 2012; 51(13): 2694-705. PubMed: 22424482
| Comments:Ishida et al (2008) found "a CaM-binding IQ-motif" beginning at I441.
Author JK MacDonald adds,
1) The IQ domain found within the ordered calponin homology (CH) domain facilitates apo-calmodulin binding.
2) The IDR proximal to CH-domain and the CH domain are required for tropomyosin binding.
|
| Region 4 | | Type: | Disordered | | Name: | C-terminal tail | | Location: | 449 - 459 | | Length: | 11 | | Region sequence: |
VQKGLVKTKKK | | Modification type: | Fragment
| | PDB: | 2JV9:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular recognition effectors
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (293 K; pH: 7; 90% H2O/10% D2O (or 100% D2O); DSS 0.5 mM; SMTNL1-CH fragment (PDB 2JV9. (0.5-1.0 mM)) 1 mM; sodium azide (0.03%); sodium phosphate 1 mM; [U-2H] DTT 10 mM)
- Circular dichroism (CD) spectroscopy, far-UV (295 K; pH: 7; CHASM-CH fragment (K346-K459) (alone or with pxIDR) 5 uM; CHASM-pxIDR fragment (L195-V345) (alone or with CH domain) 5 uM; potassium phosphate (buffer) 20 mM)
- Nuclear magnetic resonance (NMR) (293 K; pH: 6.8; Bis-Tris (buffer) 20 mM; CHASM-CH fragment (K346-K459) 0.3 mM; CHASM-pxIDR fragment (L195-V345); DSS 0.5 mM; DTT 5 mM; KCl 50 mM)
| References:
- Ishida H, Borman MA, Ostrander J, Vogel HJ, MacDonald JA. "Solution structure of the calponin homology (CH) domain from the smoothelin-like 1 protein: a unique apocalmodulin-binding mode and the possible role of the C-terminal type-2 CH-domain in smooth muscle relaxation." J. Biol. Chem.. 2008; 283(29): 20569-78. PubMed: 18477568
- MacDonald JA, Ishida H, Butler EI, Ulke-Lemée A, Chappellaz M, Tulk SE, Chik JK, Vogel HJ. "Intrinsically disordered N-terminus of calponin homology-associated smooth muscle protein (CHASM) interacts with the calponin homology domain to enable tropomyosin binding." Biochemistry. 2012; 51(13): 2694-705. PubMed: 22424482
| Comments:Ishida et al (2008) describe a unique solvent-exposed cluster at K455-K459 that "bestows a highly basic surface to the SMTNL1-CH molecule." This cluster is not found in other CH-domain-containing proteins.
|
| Comments |
Additional unreviewed UniProt (TrEMBL) entry exists for this protein, Q9D143_MOUSE, which comprises a C-terminal fragment, possibly an isoform.
AV 10-15-2012 (22424482).
|
| If you have any comments or wish to provide additional references to this protein or its disordered region(s), please click here to e-mail us. |
Disprot-footer
|
