Enrichment analyses of diseases and pathways associated with precocious puberty using PrecocityDB

Gene Information

Gene Symbol

SMAD4

Aliases

DPC4, JIP, MADH4, MYHRS

Entrez Gene ID

4089

Gene Name

SMAD family member 4

Chromosomal Location

18q21.2

HGNC ID

6770

Summary

This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasng blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Aug 2017]

RefSeq DNA

NG_013013.2

RefSeq mRNA

NM_005359.6, NM_005359.5

e!Ensembl

Gene	ENSG00000141646
Transcript	ENST00000588860, ENST00000398417, ENST00000589076, ENST00000590061, ENST00000342988, ENST00000592911, ENST00000589941, ENST00000588745, ENST00000592186, ENST00000589706, ENST00000585448, ENST00000591126, ENST00000611848, ENST00000590499, ENST00000593223, ENST00000586253
Protein	ENSP00000465878, ENSP00000381452, ENSP00000466934, ENSP00000464772, ENSP00000341551, , ENSP00000465874, ENSP00000464901, ENSP00000468611, ENSP00000478613, ENSP00000466118

SNPs

SNP	SNP ID	Associated disease	References
Ile500Val	rs281875322	Precocious puberty	31654632

Gene Ontology (GO)

Show/Hide all(54 )

GO ID	Ontology	Function	Evidence	Reference
GO:0000122	Biological process	Negative regulation of transcription by RNA polymerase II	IBA	21873635
GO:0001666	Biological process	Response to hypoxia	IMP	12411310
GO:0007179	Biological process	Transforming growth factor beta receptor signaling pathway	IBA	21873635
GO:0007179	Biological process	Transforming growth factor beta receptor signaling pathway	IDA	9389648, 9732876
GO:0007179	Biological process	Transforming growth factor beta receptor signaling pathway	IMP	25514493
GO:0007183	Biological process	SMAD protein complex assembly	IDA	10823886
GO:0009653	Biological process	Anatomical structure morphogenesis	IBA	21873635
GO:0017015	Biological process	Regulation of transforming growth factor beta receptor signaling pathway	IMP	8774881
GO:0030154	Biological process	Cell differentiation	IBA	21873635
GO:0030308	Biological process	Negative regulation of cell growth	IDA	8774881
GO:0030509	Biological process	BMP signaling pathway	IBA	21873635
GO:0030509	Biological process	BMP signaling pathway	IDA	9389648
GO:0030511	Biological process	Positive regulation of transforming growth factor beta receptor signaling pathway	IDA	19328798
GO:0030513	Biological process	Positive regulation of BMP signaling pathway	IMP	19366699
GO:0032909	Biological process	Regulation of transforming growth factor beta2 production	IMP	12411310
GO:0035556	Biological process	Intracellular signal transduction	IMP	22316667
GO:0045892	Biological process	Negative regulation of transcription, DNA-templated	IDA	8774881
GO:0045893	Biological process	Positive regulation of transcription, DNA-templated	IDA	8774881, 9311995, 9389648, 9707553, 9732876
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IDA	9389648, 18832382
GO:0060395	Biological process	SMAD protein signal transduction	IBA	21873635
GO:0060395	Biological process	SMAD protein signal transduction	IDA	9707553, 9732876
GO:0071559	Biological process	Response to transforming growth factor beta	IDA	9707553
GO:0071773	Biological process	Cellular response to BMP stimulus	NAS	14687659
GO:1901522	Biological process	Positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus	TAS	14687659
GO:0000790	Cellular component	Nuclear chromatin	IDA	21828274
GO:0005634	Cellular component	Nucleus	IDA	9311995, 9389648, 12161428, 16007207
GO:0005667	Cellular component	Transcription factor complex	IDA	17438144
GO:0005667	Cellular component	Transcription factor complex	IPI	12374795
GO:0005737	Cellular component	Cytoplasm	IBA	21873635
GO:0005737	Cellular component	Cytoplasm	IDA	9311995, 9389648, 12161428
GO:0032444	Cellular component	Activin responsive factor complex	IDA	9389648
GO:0071141	Cellular component	SMAD protein complex	IDA	18832382
GO:0071141	Cellular component	SMAD protein complex	IMP	10647180
GO:0071144	Cellular component	Heteromeric SMAD protein complex	IBA	21873635
GO:0000976	Molecular function	Transcription regulatory region sequence-specific DNA binding	IDA	17438144
GO:0000978	Molecular function	RNA polymerase II proximal promoter sequence-specific DNA binding	IBA	21873635
GO:0000978	Molecular function	RNA polymerase II proximal promoter sequence-specific DNA binding	IDA	9389648, 18832382, 31582430
GO:0000981	Molecular function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISM	19274049
GO:0001223	Molecular function	Transcription coactivator binding	IPI	16777850
GO:0001228	Molecular function	DNA-binding transcription activator activity, RNA polymerase II-specific	IBA	21873635
GO:0001228	Molecular function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	9389648, 18832382
GO:0003677	Molecular function	DNA binding	IDA	9389648
GO:0003700	Molecular function	DNA-binding transcription factor activity	IDA	10823886, 17438144
GO:0005515	Molecular function	Protein binding	IPI	9389648, 9436979, 9707553, 11278302, 11779505, 12419246, 14525983, 14612439, 14671321, 15084259, 15231748, 15350224, 15781469, 16189514, 16865698, 17099224, 17183365, 17469184, 18511908, 18568018, 18729074, 18832382, 19032343, 19135894, 20603019, 21297662, 21532621, 21597466, 219888
GO:0008134	Molecular function	Transcription factor binding	IBA	21873635
GO:0031625	Molecular function	Ubiquitin protein ligase binding	IBA	21873635
GO:0042802	Molecular function	Identical protein binding	IPI	9111321, 10647180, 21988832, 25609649
GO:0042803	Molecular function	Protein homodimerization activity	IPI	8774881
GO:0043199	Molecular function	Sulfate binding	IMP	10647180
GO:0043565	Molecular function	Sequence-specific DNA binding	IDA	10823886
GO:0070411	Molecular function	I-SMAD binding	IBA	21873635
GO:0070411	Molecular function	I-SMAD binding	IPI	9256479
GO:0070412	Molecular function	R-SMAD binding	IPI	8774881, 9111321, 9311995, 9732876

Protein Information

Protein Name

Mothers against decapentaplegic homolog 4, MAD homolog 4, SMAD, mothers against DPP homolog 4, deleted in pancreatic carcinoma locus 4, deletion target in pancreatic carcinoma 4, mothers against decapentaplegic, Drosophila, homolog of, 4

Function

Refseq Proteins

NP_005350.1

UniProt

Q13485

PDB

1DD1, 1G88, 1MR1, 1U7F, 1U7V, 1YGS, 5C4V, 5MEY, 5MEZ, 5MF0, 5UWU