Reviewed, UniProtKB/Swiss-Prot O70436 (SMAD2_RAT)

Names and origin

Protein names

Recommended name:
    Mothers against decapentaplegic homolog 2
      Short name=Mothers against DPP homolog 2
Alternative name(s):
    Mad-related protein 2
    SMAD 2

Gene names

Name:	Smad2
Synonyms:	Madh2

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	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Transcriptional modulator activated by TGF-beta and activin type 1 receptor kinase. SMAD2 is a receptor-regulated SMAD (R-SMAD).
Subunit structure	Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with SMAD3 and TRIM33. Interacts with SARA (SMAD anchor for receptor activation); may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300 and SKI. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts (via PY-motif) with SMURF2. Interacts with AIP1 and HGS. Interacts with NEDD4L in response to TGF-beta. Interacts with LBXCOR1 and CORL2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3 By similarity.
Subcellular location	Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.
Post-translational modification	In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. Able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin By similarity. In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation By similarity. Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity 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 Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	anterior/posterior pattern formation Inferred from sequence or structural similarity. Source: UniProtKB cell fate commitment Inferred from sequence or structural similarity. Source: UniProtKB intracellular signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB mesoderm formation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype. Source: RGD paraxial mesoderm morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB regulation of binding Inferred from sequence or structural similarity. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: RGD transcription factor complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	double-stranded DNA binding Inferred from sequence or structural similarity. Source: UniProtKB transcription activator activity Inferred from sequence or structural similarity. Source: UniProtKB transcription factor activity Inferred from electronic annotation. Source: InterPro transcription factor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 467	466	Mothers against decapentaplegic homolog 2		PRO_0000090854
Regions
	Domain	10 – 176	167	MH1
	Domain	274 – 467	194	MH2
	Motif	221 – 225	5	PY-motif By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	8	1	Phosphothreonine By similarity
	Modified residue	19	1	N6-acetyllysine By similarity
	Modified residue	240	1	Phosphoserine; by CAMK2 By similarity
	Modified residue	458	1	Phosphoserine By similarity
	Modified residue	465	1	Phosphoserine By similarity
	Modified residue	467	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	O70436-1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 3A775444411F6619	FASTA	467	52,239
	10 20 30 40 50 60 MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK KLKKTGRLDE 70 80 90 100 110 120 LEKAITTQNC NTKCVTIPST CSEIWGLSTA NTVDQWDTTG LYSFSEQTRS LDGRLQVSHR 130 140 150 160 170 180 KGLPHVIYCR LWRWPDLHSH HELKAIENCE YAFSLKKDEV CVNPYHYQRV ETPVLPPVLV 190 200 210 220 230 240 PRHTEILTEL PPLDDYTHSI PENTNFPAGI EPQSNYIPET PPPGYISEDG ETSDQQLNQS 250 260 270 280 290 300 MDTGSPAELS PTTLSPVNHS LDLQPVTYSE PAFWCSIAYY ELNQRVGETF HASQPSLTVD 310 320 330 340 350 360 GFTDPSNSER FCLGLLSNVN RNATVEMTRR HIGRGVRLYY IGGEVFAECL SDSAIFVQSP 370 380 390 400 410 420 NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF AALLAQSVNQ GFEAVYQLTR MCTIRMSFVK 430 440 450 460 GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD KVLTQMGSPS VRCSSMS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Involvement of Smad proteins in the differentiation of pancreatic AR42J cells induced by activin A." Zhang Y.-Q., Kanzaki M., Furukawa M., Shibata H., Ozeki M., Kojima I. Diabetologia 42:719-727(1999) [PubMed: 10382592] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Brain.
[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].
[3]	"Molecular cloning of rat Smad2 gene." Miyakita A., Okuno S., Watanabe T.K., Oga K., Tsuji A., Hishigaki H., Kato S., Sano A., Suto T., Nakagawa K., Nakahara Y., Haraguchi N., Higashi K. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB017912 mRNA. Translation: BAA33453.1. AF056001 mRNA. Translation: AAC12780.1. AB010147 mRNA. Translation: BAA81909.1. BC127497 mRNA. Translation: AAI27498.1.
IPI	IPI00198544.
RefSeq	NP_062064.1.
UniGene	Rn.2755
3D structure databases
HSSP	HSSP built from PDB template 1KHX based on UniProtKB Q15796.
SMR	O70436. Positions 263-456.
ModBase	Search...
Protein-protein interaction databases
STRING	O70436.
PTM databases
PhosphoSite	O70436.
Genome annotation databases
Ensembl	ENSRNOT00000039749; ENSRNOP00000036431; ENSRNOG00000018140; Rattus norvegicus. [Genome view] ENSRNOT00000046847; ENSRNOP00000048329; ENSRNOG00000018140; Rattus norvegicus. [Genome view]
GeneID	29357.
KEGG	rno:29357.
UCSC	NM_019191. rat.
Organism-specific databases
CTD	29357.
RGD	3031. Smad2.
Phylogenomic databases
HOVERGEN	O70436.
OMA	WKKSASG.
Gene expression databases
ArrayExpress	O70436.
Genevestigator	O70436.
GermOnline	ENSRNOG00000018140. 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	608870.

Entry information

Entry name

SMAD2_RAT

Accession

Primary (citable) accession number: O70436
Secondary accession number(s): A0JPM1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	August 1, 1998
Last modified:	November 3, 2009
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)