SG00001885

SpermatogenesisOnline 1.0

Tag

Content

SG ID

SG00001885

UniProt Accession

SMAD3_RAT;P84025;O09064;O09144;O14510;O35273;Q92940;Q93002;Q9GKR4;

Theoretical PI

6.73

Molecular Weight

48081 Da

Genbank Nucleotide ID

U66479; BC064437;

Genbank Protein ID

AAC52944.1; AAH64437.1;

Gene Name

Smad3

Gene Synonyms/Alias

Madh3

Protein Name

Mothers against decapentaplegic homolog 3

Protein Synonyms/Alias

MAD homolog 3Mad3Mothers against DPP homolog 3 SMAD family member 3;SMAD 3Smad3

Organism

Rattus norvegicus (Rat)

NCBI Taxonomy ID

10116

Chromosome Location

chr:8;67803914-67952056;-1

View in Ensembl genome browser

Function in Stage

meiotic

Function in Cell Type

spermatocyte

leydig_cell

sertoli_cell

Description

Temporarily unavailable

The information of related literatures

1. J. Xu, A. R. Beyer, W. H. Walker and E. A. McGee (2003) Developmental and stage-specific expression of Smad2 and Smad3 in rat testis. J Androl 24(2): 192-200.

Abstract
Members of the transforming growth factor beta type (TGFbeta) superfamily and their receptors are expressed in the testis, and are believed to play important paracrine and autocrine roles during testicular development and spermatogenesis. The Smad proteins are downstream mediators for the family of TGFbeta growth factors. Smad2 and Smad3 are associated with both TGFbeta and activin signaling. However, very little is known about the expression and regulation of the Smad signaling proteins in the testis. In the present study, we have determined that Smad2 and Smad3 proteins are expressed in the postnatal testes of rats from 5 days to 60 days of age. Expression levels for both proteins are higher in young rats than in sexually mature rats. Smad2 and Smad3 messenger RNA levels parallel protein expression. Smad2 and Smad3 proteins are mainly localized in the cytoplasm of meiotic germ cells, Sertoli cells, and Leydig cells. Smad3 protein is localized to the nucleus of preleptotene to zygotene primary spermatocytes in young rats. Both proteins are expressed throughout all stages of the cycle of seminiferous tubules but are expressed at their lowest levels at stages VII-VIII in the seminiferous epithelium of adult rats. The presence of these downstream mediators in these cell types supports a role for TGFbeta and activin during spermatogenesis. The difference between the expression of Smad2 and Smad3 suggests that they may have different functions within the testis. PMID: [12634305]

Figures for illustrating the function of this protein/gene

	Ref: J. Xu, A. R. Beyer, W. H. Walker and E. A. McGee (2003) Developmental and stage-specific expression of Smad2 and Smad3 in rat testis. J Androl 24(2): 192-200. PMID: [12634305]
	Ref: J. Xu, A. R. Beyer, W. H. Walker and E. A. McGee (2003) Developmental and stage-specific expression of Smad2 and Smad3 in rat testis. J Androl 24(2): 192-200. PMID: [12634305]

Function

Receptor-regulated SMAD (R-SMAD) that is anintracellular signal transducer and transcriptional modulatoractivated by TGF-beta (transforming growth factor) and activintype 1 receptor kinases. Binds the TRE element in the promoterregion of many genes that are regulated by TGF-beta and, onformation of the SMAD3/SMAD4 complex, activates transcription.Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD siteto regulate TGF-beta-mediated transcription. Has an inhibitoryeffect on wound healing probably by modulating both growth andmigration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healingappears to be hormone-sensitive. Regulator of chondrogenesis andosteogenesis and inhibits early healing of bone fractures.Positively regulates PDPK1 kinase activity by stimulating itsdissociation from the 14-3-3 protein YWHAQ which acts as anegative regulator (By similarity).

Subcellular Location

Cytoplasm (By similarity). Nucleus.Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed withSMAD4. Through the action of the phosphatase PPM1A, released fromthe SMAD2/SMAD4 complex, and exported out of the nucleus byinteraction with RANBP1. Co-localizes with LEMD3 at the nucleusinner membrane. MAPK-mediated phosphorylation appears to have noeffect on nuclear import. PDPK1 prevents its nuclear translocationin response to TGF-beta (By similarity).

Tissue Specificity

Highly expressed in the brain and ovary.Detected in the pyramidal cells of the hippocampus, granule cellsof the dentate gyrus, granular cells of the cerebral cortex andthe granulosa cells of the ovary.

Gene Ontology

GO ID	GO term	Evidence
GO:0005737	C:cytoplasm	IDA:RGD.
GO:0005637	C:nuclear inner membrane	IEA:Compara.
GO:0005886	C:plasma membrane	IEA:Compara.
GO:0043235	C:receptor complex	IEA:Compara.
GO:0071141	C:SMAD protein complex	IEA:Compara.
GO:0005667	C:transcription factor complex	IDA:RGD.
GO:0031490	F:chromatin DNA binding	IEA:Compara.
GO:0000987	F:core promoter proximal region sequence-specific DNA binding	IEA:Compara.
GO:0003690	F:double-stranded DNA binding	IEA:Compara.
GO:0000988	F:protein binding transcription factor activity	IEA:Compara.
GO:0043565	F:sequence-specific DNA binding	IDA:RGD.
GO:0003700	F:sequence-specific DNA binding transcription factor activity	IDA:RGD.
GO:0030618	F:transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity	IEA:Compara.
GO:0008270	F:zinc ion binding	IEA:Compara.
GO:0006919	P:activation of cysteine-type endopeptidase activity involved in apoptotic process	IEA:Compara.
GO:0008633	P:activation of pro-apoptotic gene products	IMP:RGD.
GO:0007050	P:cell cycle arrest	IEA:Compara.
GO:0045216	P:cell-cell junction organization	IEA:Compara.
GO:0048589	P:developmental growth	IEA:Compara.
GO:0048701	P:embryonic cranial skeleton morphogenesis	IEA:Compara.
GO:0048617	P:embryonic foregut morphogenesis	IEA:Compara.
GO:0009880	P:embryonic pattern specification	IEA:Compara.
GO:0007492	P:endoderm development	IEA:Compara.
GO:0019049	P:evasion or tolerance of host defenses by virus	IEA:Compara.
GO:0001947	P:heart looping	IEA:Compara.
GO:0006955	P:immune response	IEA:Compara.
GO:0002520	P:immune system development	IEA:Compara.
GO:0001701	P:in utero embryonic development	IEA:Compara.
GO:0006917	P:induction of apoptosis	IEA:Compara.
GO:0070306	P:lens fiber cell differentiation	IEA:Compara.
GO:0001889	P:liver development	IEA:Compara.
GO:0001707	P:mesoderm formation	IEA:Compara.
GO:0043066	P:negative regulation of apoptotic process	IDA:RGD.
GO:0030308	P:negative regulation of cell growth	IEA:Compara.
GO:0008285	P:negative regulation of cell proliferation	IDA:RGD.
GO:0050728	P:negative regulation of inflammatory response	IEA:Compara.
GO:0045930	P:negative regulation of mitotic cell cycle	IEA:Compara.
GO:0045668	P:negative regulation of osteoblast differentiation	IEA:Compara.
GO:0033689	P:negative regulation of osteoblast proliferation	IEA:Compara.
GO:0042177	P:negative regulation of protein catabolic process	IEA:Compara.
GO:0001933	P:negative regulation of protein phosphorylation	IEA:Compara.
GO:0000122	P:negative regulation of transcription from RNA polymerase II promoter	IMP:RGD.
GO:0061045	P:negative regulation of wound healing	IEA:Compara.
GO:0038092	P:nodal signaling pathway	IEA:Compara.
GO:0002076	P:osteoblast development	IEA:Compara.
GO:0048340	P:paraxial mesoderm morphogenesis	IEA:Compara.
GO:0060039	P:pericardium development	IEA:Compara.
GO:0010694	P:positive regulation of alkaline phosphatase activity	IDA:RGD.
GO:0030501	P:positive regulation of bone mineralization	IDA:RGD.
GO:0090263	P:positive regulation of canonical Wnt receptor signaling pathway	IEA:Compara.
GO:0035413	P:positive regulation of catenin import into nucleus	IEA:Compara.
GO:0030335	P:positive regulation of cell migration	IMP:RGD.
GO:0032332	P:positive regulation of chondrocyte differentiation	IEA:Compara.
GO:0010718	P:positive regulation of epithelial to mesenchymal transition	IEA:Compara.
GO:0051894	P:positive regulation of focal adhesion assembly	IDA:RGD.
GO:0032731	P:positive regulation of interleukin-1 beta production	IMP:RGD.
GO:0050927	P:positive regulation of positive chemotaxis	IDA:RGD.
GO:0051496	P:positive regulation of stress fiber assembly	IDA:RGD.
GO:0042993	P:positive regulation of transcription factor import into nucleus	IEA:Compara.
GO:0045944	P:positive regulation of transcription from RNA polymerase II promoter	IDA:RGD.
GO:0032916	P:positive regulation of transforming growth factor beta3 production	IMP:RGD.
GO:0050821	P:protein stabilization	IEA:Compara.
GO:0051098	P:regulation of binding	IEA:Compara.
GO:0050678	P:regulation of epithelial cell proliferation	IEA:Compara.
GO:0050776	P:regulation of immune response	IEA:Compara.
GO:0016202	P:regulation of striated muscle tissue development	IEA:Compara.
GO:0017015	P:regulation of transforming growth factor beta receptor signaling pathway	IEA:Compara.
GO:0032909	P:regulation of transforming growth factor beta2 production	IEA:Compara.
GO:0001836	P:release of cytochrome c from mitochondria	IMP:RGD.
GO:0001666	P:response to hypoxia	IEA:Compara.
GO:0007183	P:SMAD protein complex assembly	IPI:RGD.
GO:0001756	P:somitogenesis	IEA:Compara.
GO:0042110	P:T cell activation	IEA:Compara.
GO:0030878	P:thyroid gland development	IEA:Compara.
GO:0006351	P:transcription, DNA-dependent	IEA:UniProtKB-KW.
GO:0060290	P:transdifferentiation	IDA:RGD.
GO:0007179	P:transforming growth factor beta receptor signaling pathway	IMP:RGD.
GO:0006810	P:transport	IEA:Compara.
GO:0001657	P:ureteric bud development	IEA:Compara.

Interpro

IPR013790;    Dwarfin.
IPR003619;    MAD_homology1_Dwarfin-type.
IPR013019;    MAD_homology_MH1.
IPR017855;    SMAD_dom-like.
IPR001132;    SMAD_dom_Dwarfin-type.
IPR008984;    SMAD_FHA_domain.
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Pfam

PF03165; MH1; 1.
PF03166; MH2; 1.
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SMART

SM00523; DWA; 1.
SM00524; DWB; 1.
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PROSITE

PS51075; MH1; 1.
PS51076; MH2; 1.
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PRINTS

Created Date

18-Oct-2012

Record Type

Experiment identified

Protein sequence Annotation

CHAIN         1    425       Mothers against decapentaplegic homolog
                             3.
                             /FTId=PRO_0000090859.
DOMAIN       10    136       MH1.
DOMAIN      232    425       MH2.
REGION      137    231       Linker.
REGION      271    324       Sufficient for interaction with XPO4 (By
                             similarity).
METAL        64     64       Zinc (By similarity).
METAL       109    109       Zinc (By similarity).
METAL       121    121       Zinc (By similarity).
METAL       126    126       Zinc (By similarity).
SITE         40     40       Required for trimerization (By
                             similarity).
SITE         41     41       Required for interaction with DNA and JUN
                             and for functional cooperation with JUN
                             (By similarity).
MOD_RES       8      8       Phosphothreonine; by CDK2 and CDK4 (By
                             similarity).
MOD_RES     179    179       Phosphothreonine; by CDK2, CDK4 and MAPK
                             (By similarity).
MOD_RES     204    204       Phosphoserine; by GSK3 and MAPK (By
                             similarity).
MOD_RES     208    208       Phosphoserine; by MAPK (By similarity).
MOD_RES     213    213       Phosphoserine; by CDK2 and CDK4 (By
                             similarity).
MOD_RES     378    378       N6-acetyllysine (By similarity).
MOD_RES     416    416       Phosphoserine (By similarity).
MOD_RES     418    418       Phosphoserine; by CK1 (By similarity).
MOD_RES     422    422       Phosphoserine; by TGFBR1 (By similarity).
MOD_RES     423    423       Phosphoserine; by TGFBR1 (By similarity).
MOD_RES     425    425       Phosphoserine; by TGFBR1 (By similarity).
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Nucleotide Sequence

Length: 1312 bp Go to nucleotide: FASTA

Protein Sequence

Length: 425 bp Go to amino acid: FASTA

The verified Protein-Protein interaction information

UniProt	Gene Symbol	Ref Databases
AKT1_RAT	Akt1	MINT
Q7TP68_RAT	Zeb1	BioGRID
AKT1_RAT	Akt1	MINT
Q7TP68_RAT	Zeb1	BioGRID

Other Protein-Protein interaction resources

String database

View Microarray data

Temporarily unavailable

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