Annotation for this protein is in progress - please check future releases for more complete information


DP00464: Mothers against decapentaplegic homolog 4FASTA viewXML view

General information
DisProt:DP00464
Name:Mothers against decapentaplegic homolog 4
Synonym(s):SMAD4_HUMAN
Mothers against DPP homolog 4
SMAD 4
hSMAD4
Deletion target in pancreatic carcinoma 4
First appeared in release:Release 3.1 (03/31/2006)
UniProt:Q13485
UniGene:Hs.75862
SwissProt: SMAD4_HUMAN
TrEMBL:  
NCBI (GI): 13959561
Source organism:Homo sapiens (Human)
Sequence length:552
Percent disordered:11%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MDNMSITNTP TSNDACLSIV HSLMCHRQGG ESETFAKRAI ESLVKKLKEK KDELDSLITA - 60
ITTNGAHPSK CVTIQRTLDG RLQVAGRKGF PHVIYARLWR WPDLHKNELK HVKYCQYAFD - 120
LKCDSVCVNP YHYERVVSPG IDLSGLTLQS NAPSSMMVKD EYVHDFEGQP SLSTEGHSIQ - 180
TIQHPPSNRA STETYSTPAL LAPSESNATS TANFPNIPVA STSQPASILG GSHSEGLLQI - 240
ASGPQPGQQQ NGFTGQPATY HHNSTTTWTG SRTAPYTPNL PHHQNGHLQH HPPMPPHPGH - 300
YWPVHNELAF QPPISNHPAP EYWCSIAYFE MDVQVGETFK VPSSCPIVTV DGYVDPSGGD - 360
RFCLGQLSNV HRTEAIERAR LHIGKGVQLE CKGEGDVWVR CLSDHAVFVQ SYYLDREAGR - 420
APGDAVHKIY PSAYIKVFDL RQCHRQMQQQ AATAQAAAAA QAAAVAGNIP GPGSVGGIAP - 480
AISLSAAAGI GVDDLRRLCI LRMSFVKGWG PDYPRQSIKE TPCWIEIHLH RALQLLDEVL - 540
HTMPIADPQP LD



Functional narrative    

Common mediator of signal transduction by TGF-beta (transforming growth factor) superfamily; SMAD4 is the common SMAD (co-SMAD). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. May act as a tumor suppressor.

Region 1: 273-284 Region 8: 273-284 Region 5: 273-284 Region 6: 297-306 Region 2: 297-310 Region 9: 295-311 Region 10: 469-478 Region 7: 470-478 Region 3: 461-486 Region 4: 546-552

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:subunit A
Location:273 - 284
Length:12
Region sequence:

TAPYTPNLPHHQ

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Transactivation (transcriptional activation)
Protein-protein binding
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; PEG 4000 (10%); LiSO4 200 mM)
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 2
Type:Disordered
Name:subunit A
Location:297 - 310
Length:14
Region sequence:

HPGHYWPVHNELAF

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Transactivation (transcriptional activation)
Protein-protein binding
Intraprotein interaction
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10 %))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 3
Type:Disordered
Name:subunit A
Location:461 - 486
Length:26
Region sequence:

QAAAVAGNIPGPGSVGGIAPAISLSA

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Transactivation (transcriptional activation)
Protein-protein binding
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10%))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 4
Type:Disordered
Name:subunit A
Location:546 - 552
Length:7
Region sequence:

ADPQPLD

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10%))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 5
Type:Disordered
Name:subunit B
Location:273 - 284
Length:12
Region sequence:

TAPYTPNLPHHQ

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Transactivation (transcriptional activation)
Protein-protein binding
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10%))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 6
Type:Disordered
Name:subunit B
Location:297 - 306
Length:10
Region sequence:

HPGHYWPVHN

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Transactivation (transcriptional activation)
Protein-protein binding
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10%))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 7
Type:Disordered
Name:subunit B
Location:470 - 478
Length:9
Region sequence:

PGPGSVGGI

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10 %))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 8
Type:Disordered
Name:subunit C
Location:273 - 284
Length:12
Region sequence:

TAPYTPNLPHHQ

Modification type: Fragment
PDB:  
Structural/functional type: Function arises via an order to disorder transition
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Transactivation (transcriptional activation)
Protein-protein binding
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10%))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 9
Type:Disordered
Name:subunit C
Location:295 - 311
Length:17
Region sequence:

PPHPGHYWPVHNELAFQ

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Transactivation (transcriptional activation)
Protein-protein binding
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10%))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



Region 10
Type:Disordered
Name:subunit C
Location:469 - 478
Length:10
Region sequence:

IPGPGSVGGI

Modification type: Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Intraprotein interaction
Detection methods:
  1. X-ray crystallography (298 K; HEPES (pH 7) 100 mM; LiSO4 200 mM; PEG 4000 (10%))
References:
  1. Qin B, Lam SS, Lin K. "Crystal structure of a transcriptionally active Smad4 fragment." Structure. 1999; 7(12): 1493-503. PubMed: 10647180
Comments:
 



References

  1. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE. "DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1." Science. 1996; 271(5247): 350-3. PubMed: 8553070



Comments


The active Smad4 fragment forms an asymmetric trimer that consists of 3 non-quivalent subunits based on different degrees of disorder. Disorder regions 1-4 belong to subunit A, disorder regions 5-7 belong to subunit B, and disorder regions 8-10 belong to subunit C.


In the experiment, the crystal structure of the transcriptionally active Smad4 fragment (residues 273- 552) is analyzed. It consists of the Smad4 activation domain and the MH2 domain.


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