Reviewed, UniProtKB/Swiss-Prot O70437 (SMAD4_RAT)

Names and origin

Protein names

Recommended name:
    Mothers against decapentaplegic homolog 4
      Short name=Mothers against DPP homolog 4
Alternative name(s):
    SMAD 4
      Short name=Smad4

Gene names

Name:	Smad4
Synonyms:	Madh4

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	552 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Common mediator of signal transduction by TGF-beta (transforming growth factor) superfamily; SMAD4 is the common SMAD (co-SMAD) By similarity.
Subunit structure	May form trimers with receptor-regulated SMAD (R-SMAD). Found in a ternary complex composed of SMAD4, STK11 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11, STK11IP and TRIM33. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with USP9X By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with R-SMAD By similarity.
Post-translational modification	Monoubiquitinated on Lys-519 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade By similarity.
Sequence similarities	Belongs to the dwarfin/SMAD family. Contains 1 MH1 (MAD homology 1) domain. Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
PTM	Acetylation Isopeptide bond Ubl conjugation
Gene Ontology (GO)
Biological process	transcription Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: RGD transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular function	SMAD binding Inferred from physical interaction. Source: RGD transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 552	552	Mothers against decapentaplegic homolog 4		PRO_0000090864
Regions
	Domain	18 – 142	125	MH1
	Domain	323 – 552	230	MH2
	Region	275 – 320	46	SAD
	Compositional bias	451 – 466	16	Poly-Ala
Amino acid modifications
	Modified residue	37	1	N6-acetyllysine By similarity
	Modified residue	428	1	N6-acetyllysine By similarity
	Modified residue	507	1	N6-acetyllysine By similarity
	Cross-link	519		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

	Sequence		Length	Mass (Da)
	O70437-1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 7AE0540AB4DF0E77	FASTA	552	60,469
	10 20 30 40 50 60 MDNMSITNTP TSNDACLSIV HSLMCHRQGG ESETFAKRAI ESLVKKLKEK KDELDSLITA 70 80 90 100 110 120 ITTNGAHPSK CVTIQRTLDG RLQVAGRKGF PHVIYARLWR WPDLHKNELK HVKYCQYAFD 130 140 150 160 170 180 LKCDSVCVNP YHYERVVSPG IDLSGLTLQS NAPPSMLVKD EYVHDFEGQP SLPTEGHSIQ 190 200 210 220 230 240 TIQHPPSNRA STETYSAPAL LAPSESNATS TTNFPNIPVA STSQPASILA GSHSEGLLQI 250 260 270 280 290 300 ASGPQPGQQQ NGFTAQPATY HHNSTTTWTG SRTAPYTPNL PHHQNGHLQH HPPMPPHPGH 310 320 330 340 350 360 YWPVHNELAF QPPISNHPAP EYWCSIAYFE MDVQVGETFK VPSSCPIVTV DGYVDPSGGD 370 380 390 400 410 420 RFCLGQLSNV HRTEAIERAR LHIGKGVQLE CKGEGDVWVR CLSDHAVFVQ SYYLDREAGR 430 440 450 460 470 480 APGDAVHKIY PSAYIKVFDL RQCHRQMQQQ AATAQAAAAA QAAAVAGNIP GPGSVGGIAP 490 500 510 520 530 540 AISLSAAAGI GVDDLRRLCI LRMSFVKGWG PDYPRQSIKE TPCWIEIHLH RALQLLDEVL 550 HTMPIADPQP LD

References

[1]	"Molecular cloning of rat Smad4 gene." Miyakita A., Okuno S., Watanabe T.K., Oga K., Tsuji A., Hishigaki H., Suto T., Nakagawa K., Nakahara Y., Higashi K. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[2]	"cDNA cloning and chromosomal mapping of rat Smad2 and Smad4 and their expression in cultured rat articular chondrocytes." Osaki M., Tsukazaki T., Ono N., Yonekura A., Hirota Y., Miyazaki Y., Shindo H., Sonta S., Yamashita S. Endocr. J. 46:695-701(1999) [PubMed: 10670756] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB010954 mRNA. Translation: BAA83092.1. AF056002 mRNA. Translation: AAC12781.1.
IPI	IPI00198545.
RefSeq	NP_062148.1.
UniGene	Rn.9774
3D structure databases
HSSP	HSSP built from PDB template 1DD1 based on UniProtKB Q13485.
SMR	O70437. Positions 295-552.
ModBase	Search...
Protein-protein interaction databases
STRING	O70437.
Genome annotation databases
Ensembl	ENSRNOT00000021113; ENSRNOP00000021113; ENSRNOG00000015634; Rattus norvegicus. [Genome view]
GeneID	50554.
KEGG	rno:50554.
UCSC	NM_019275. rat.
Organism-specific databases
CTD	50554.
RGD	3033. Smad4.
Phylogenomic databases
HOVERGEN	O70437.
Gene expression databases
ArrayExpress	O70437.
Genevestigator	O70437.
GermOnline	ENSRNOG00000015634. Rattus norvegicus.
Family and domain databases
InterPro	IPR013790. Dwarfin. IPR003619. MAD_homology1_Dwarfin-type. IPR013019. MAD_homology_MH1. IPR017855. SMAD_dom-like. IPR001132. SMAD_dom_Dwarfin-type. [Graphical view]
Gene3D	G3DSA:3.90.520.10. MAD_MH1. 1 hit. G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.
PANTHER	PTHR13703. Dwarfin. 1 hit.
Pfam	PF03165. MH1. 1 hit. PF03166. MH2. 1 hit. [Graphical view]
SMART	SM00523. DWA. 1 hit. SM00524. DWB. 1 hit. [Graphical view]
PROSITE	PS51075. MH1. 1 hit. PS51076. MH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	610352.

Entry information

Entry name

SMAD4_RAT

Accession

Primary (citable) accession number: O70437

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 4, 2001
Last sequence update:	August 1, 1998
Last modified:	October 13, 2009
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)