V3 here soon-try beta now


Gene Search (GeneCards Home)	\|	GeneCards Guide	\|	User Feedback	\|	Terms of Use	\|	Notice about third-party sites

SMAD4 Gene

protein-coding GIFtS: 71

GC18P046810

SMAD family member 4
(Previous names: MAD, mothers against decapentaplegic homolog 4 (Drosophila), SMAD, mothers against DPP homolog 4 (Drosophila) )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database
(Previous symbol: MADH4)

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase)
About This Section

Aliases
DPC4 ^¹, ², ³, ⁵
JIP ^², ⁵
MADH4 ^², ³, ⁵
OTTHUMP00000163548 ^²
hSMAD4 ^³

Descriptions
Deletion target in pancreatic carcinoma 4 ^³
MAD, mothers against decapentaplegic homolog 4 ^²
MAD, mothers against decapentaplegic homolog 4 (Drosophila) ^¹
Mothers against DPP homolog 4 ^³
SMAD 4 ^³
SMAD family member 4 ^²
SMAD, mothers against DPP homolog 4 ^²
SMAD, mothers against DPP homolog 4 (Drosophila) ^¹
deleted in pancreatic carcinoma locus 4 ^²
mothers against decapentaplegic homolog 4 ^²
mothers against decapentaplegic, Drosophila, homolog of, 4 ^²

External Ids
HGNC: 6770¹
Entrez Gene: 4089²
UniProtKB: Q13485³
Ensembl: ENSG00000141646⁷

Search outside databases for aliases for SMAD4 gene

Previous GC identifer: GC18P046809

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

UniProtKB/Swiss-Prot: SMAD4_HUMAN, Q13485

Function: 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

Gene Wiki entry for SMAD4 (Mothers_against_decapentaplegic_homolog_4)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

Genomic View:

UCSC Golden Path with GeneCards custom track

Transcription factor binding sites upstream to the SMAD4 gene

Entrez Gene cytogenetic band: 18q21.1 Ensembl cytogenetic band: 18q21.2 HGNC cytogenetic band: 18q21.1

SMAD4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 18 GeneLoc Exon Structure

GeneLoc location for GC18P046810: (about GC identifiers)

Start:	46,810,611 bp from pter
End:	46,865,413 bp from pter
Size:	54,803 bases
Orientation:	plus strand

RefSeq DNA sequence:

NC_000018.8 NT_010966.13

(According to ¹UniProtKB, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
About This Section

UniProtKB/Swiss-Prot: SMAD4_HUMAN, Q13485 (See protein sequence)

Recommended Name: Mothers against decapentaplegic homolog 4

Size: 552 amino acids; 60439 Da

Subunit: 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

Subcellular location: Cytoplasm. Nucleus. Note=Cytoplasmic in the absence of ligand. Migrates to

the nucleus when complexed with R-SMAD

PDB structures from and Proteopedia :

1DD1 (3D)

1G88 (3D)

1MR1 (3D)

1U7F (3D)

1U7V (3D)

1YGS (3D)

Post-translational modifications:

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 cascade¹

View phosphorylation sites using PhosphoSite²

REFSEQ proteins: NP_005350.1

ENSEMBL proteins:

ENSP00000381452 ENSP00000341551

Human Recombinant Proteins

	Browse Drug Discovery Central at Invitrogen for human recombinant proteins
	Browse Purified and Recombinant Proteins at Millipore
	Sigma-Aldrich CompoZr ZFN and AQUA Peptides for SMAD4
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Recombinant Proteins from Abcam (Smad4)
	Human Recombinant Proteins from Abnova (SMAD4)

OriGene Purified Recombinant Human Protein: SMAD4

5/6 Gene Ontology (GO) cellular component terms (links to tree view) (see all 6 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	IEA	--
GO:0005634	nucleus	IEA	--
GO:0005654	nucleoplasm	EXP	10549282 11121043
GO:0005737	cytoplasm	IEA	--
GO:0005829	cytosol	EXP	9311995

About this table

Antibodies for SMAD4:

	Invitrogen Antibodies for SMAD4
	Millipore Mono- and Polyclonal Antibodies for the study of SMAD4
	Sigma-Aldrich Antibody Arrays and Antibodies for SMAD4
	R&D Systems Antibodies for SMAD4
	Cell Signaling Technology (CST) Antibodies for SMAD4
	Antibodies from Abcam (Smad4), each with their Abpromise^SM
	Monoclonal and Polyclonal Antibodies from Abnova (SMAD4)
	Novus Biologicals Antibodies for SMAD4

Assays for SMAD4:

	Browse Invitrogen for biochemical assays
	Browse Kits and Assays available from Millipore
	Browse R&D Systems for biochemical assays
	Browse biochemical assays available from Enzo Life Sciences

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

Graphical View of Domain Structure for InterPro Entry Q13485

ProtoNet protein and cluster: Q13485

1 Blocks protein family: IPB001132 Dwarfin protein

UniProtKB/Swiss-Prot: SMAD4_HUMAN, Q13485

Similarity: Belongs to the dwarfin/SMAD family

Similarity: Contains 1 MH1 (MAD homology 1) domain

Similarity: Contains 1 MH2 (MAD homology 2) domain

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (SMAD4)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (SMAD4)

OriGene 29mer shRNA kit in GFP-retroviral vector: NM_005359

Applied Biosystems Silencer® siRNAs for SMAD4

Sigma-Aldrich siRNA for SMAD4

Sigma-Aldrich shRNA Panels and shRNA for SMAD4

Explore Sigma-Aldrich super-pooled esiRNAs

Clones:		Invitrogen Clones for SMAD4
		Browse Clones for the Expression of Recombinant Proteins Available from Millipore

OriGene GFP tagged cDNA clone in CMV expression vector: NM_005359
Myc/DDK tagged cDNA clone in CMV expression vector: NM_005359
untagged cDNA clone in CMV expression vector: NM_005359

Primers:

Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers

OriGene genome-wide validated SYBR primer pairs: NM_005359

UniProtKB/Swiss-Prot: SMAD4_HUMAN, Q13485

Function: 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

15/19 MGI mutant phenotypes (inferred from 16 alleles) (MGI details for Smad4) (see all 19 ):

	behavior/neurological	cellular	digestive/alimentary	embryogenesis
endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism	immune system
lethality-postnatal	lethality-prenatal/perinatal	life span-post-weaning/aging	nervous system	normal

5/7 Gene Ontology (GO) molecular function terms (links to tree view) (see all 7 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003700	transcription factor activity	IEA	--
GO:0005518	collagen binding	IEA	--
GO:0010843	promoter binding	IDA	17438144
GO:0016563	transcription activator activity	IEA	--
GO:0030616	transforming growth factor beta receptor, common-partner cytoplasmic mediator activity	IDA	9389648

About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

5/13 Sigma-Aldrich "Your Favorite Gene" Pathways for SMAD4 (Your Favorite Gene powered by Ingenuity) (see all 13 )

Molecular Mechanisms of Cancer
BMP signaling pathway
Hepatic Fibrosis / Hepatic Stellate Cell Activation
Chronic Myeloid Leukemia Signaling
TGF-&beta

GeneDecks SMAD4 for the pathways selected above

About GeneDecksing

Gene Network Central^TM Interacting Genes and Proteins Network for SMAD4

5/285 Interacting proteins for SMAD4 (Q13485^{1, 2} ENSP00000341551³) via UniProtKB, MINT, and/or STRING (see all 285 )

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
SMAD2	Q15796², ENSP00000262160³	MINT-6799119 MINT-15900 MINT-61945 STRING (score=.999)
SMAD1	Q15797², ENSP00000305769³	MINT-62001 MINT-4298076 STRING (score=.999)
SMAD3	P84022², ENSP00000332973³	MINT-61708 MINT-61949 STRING (score=.999)
MED15	Q96RN5², ENSP00000263205³	MINT-13793 MINT-13792 STRING (score=.96)
UBE2I	P63279², ENSP00000348056³	MINT-61950 STRING (score=.995)

About this table

5/16 Gene Ontology (GO) biological process terms (links to tree view) (see all 16 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001658	ureteric bud branching	IEA	--
GO:0001666	response to hypoxia	IMP	12411310
GO:0001702	gastrulation with mouth forming second	IEA	--
GO:0001822	kidney development	IEA	--
GO:0007183	SMAD protein complex assembly	IDA	10823886

About this table

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences

Browse Small Molecules at Sigma-Aldrich

Browse Tocris compounds for SMAD4
10/13 Novoseek chemical compound relationships for SMAD4 gene (see all 13 )

Compound	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
tgf beta1	65.61	22	11784716 (4), 11196469 (2), 17469181 (2), 12935295 (2) (see all 9)
threonine	45.11	4	9312063 (1), 14656470 (1), 11889196 (1), 15702493 (1)
crcs	38.23	2	18471510 (2)
pd 98,059	24.11	1	11371552 (1)
leucine	3.40	1	11238452 (1)
nitric oxide	0.79	1	15785755 (1)
oligonucleotide	0.47	2	15107966 (1), 10753944 (1)
glucose	0.26	4	15560676 (1), 15284289 (1)
steroid	0.00	1	16350721 (1)
lead	0.00	3	17018631 (1)

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (SMAD4)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (SMAD4)

OriGene 29mer shRNA kit in GFP-retroviral vector: NM_005359

Sigma-Aldrich siRNA for SMAD4

Sigma-Aldrich shRNA Panels and shRNA for SMAD4

Explore Sigma-Aldrich super-pooled esiRNAs

Applied Biosystems Silencer® siRNAs:

NM_005359

REFSEQ mRNAs for SMAD4 gene:

NM_005359.5

Applied Biosystems TaqMan ® Gene Expression Assays:

NM_005359

              OriGene GFP tagged cDNA clone in CMV expression vector: NM_005359
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_005359
                                 untagged cDNA clone in CMV expression vector: NM_005359

Additional cDNA sequence:

AK290770.1 AK303027.1 AL832789.1 BC002379.2 BX647129.1 U44378.1

19 DOTS entries:

DT.317208 DT.121090072 DT.105413 DT.100691422 DT.40284956 DT.100001068 DT.97802720 DT.91684967

DT.121090073 DT.40264776 DT.70100794 DT.92438228 DT.92438229 DT.95078262 DT.100818887 DT.121087023

DT.92037596 DT.95370406 DT.75168357

24/272 AceView cDNA sequences (see all 272 ):

AI807344 CB217085 BX096310 AI627672 BF931218 BF430922 BM992533 BM751021

AI669235 AW169700 AL713120 BI495902 AI985283 AI928602 CA438312 AI690261

AW179300 AA972906 CD365218 F08858 CD678304 AA595745 NM_018696 AI806067

highest scoring ESTs for SMAD4:

AW021681 U44378 AW819906 CA503042 AI633288 AJ713370 AW884109 BE005008 BG991972 BI333535

Unigene Cluster for SMAD4:

SMAD family member 4

Hs.75862 [show with all ESTs]

Unigene Representative Sequence: NM_005359

GeneLoc Exon Structure

5/10 Alternative Splicing Database (ASD) splice patterns (SP) for SMAD4 (see all 10 )

ExUns:	1	^	2	^	3a	·	3b	^	4	^	5	^	6a	·	6b	·	6c	^	7a	·	7b	·	7c	^	8a	·	8b	^	9a	·	9b	^	10	^	11	^	12	^	13	^	14a	·	14b	^	15	^	16	^	17
SP1:																											-		-												-						-
SP2:																																									-						-
SP3:			-		-		-		-		-
SP4:
SP5:

About this scheme

ECgene alternative splicing isoforms for SMAD4

2 Ensembl transcripts including schematic representations:

ENST00000398417 ENST00000342988

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

SMAD4 expression in normal and diseased human tissues

Applied Biosystems TaqMan ® Gene Expression Assays for SMAD4

¹ / ² / ³

13 probe-sets matching SMAD4 gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
74813_at²^{, 3}	U95-D	1	1.00	1.00	0.66	1.71	AW021681	0.80	0.70	0.75	1
57902_at²^{, 3}	U95-C	1	1.00	1.00	0.79	0.59	AA889974	0.40	0.75	0.60	1
46885_at²	U95-B	1	1.00	1.00	0.80	0.99	--	--	--	--	--
36953_at²^{, 3}	U95-A	1	1.00	1.00	0.95	1.11	U44378	0.80	0.70	0.75	1
58962_at²^{, 3}	U95-C	1	1.00	1.00	0.72	0.77	AA745990	0.40	0.50	0.45	1
510_g_at²^{, 3}	U95-A	1	1.00	1.00	0.80	0.96	U44378	0.80	0.70	0.75	1
509_at²^{, 3}	U95-A	1	1.00	1.00	0.87	0.89	U44378	0.80	0.70	0.75	1
202527_s_at²^{, 3}	U133-A	1	1.00	1.00	--	--	NM_005359	0.40	0.50	0.45	1
235725_at²	U133-B	1	1.00	1.00	--	--	--	--	--	--	--
202526_at²^{, 3}	U133-A	1	1.00	1.00	--	--	U44378	0.80	0.70	0.75	1
202527_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
235725_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
202526_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--

GeneDecks SMAD4 for binary patterns associated with the probe-sets selected above

About GeneDecksing

About this table

Data from

(Publications) and GNF BioGPS
About these images
About these images

CGAP SAGE TAG: TATGTTATGA

SOURCE GeneReport for Unigene cluster: Hs.75862
Expression variation in blood from EXPOLDB for SMAD4

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for SMAD4 gene from 5/11 species (see all 11 )

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	SMAD4¹	--	SMAD family member 4	94.44(n) 97.44(a)	476196 XM_533400.2 XP_533400.2
chimpanzee (Pan troglodytes)	SMAD4¹	--	SMAD family member 4	99.76(n) 100(a)	468537 XM_001155350.1 XP_001155350.1
cow (Bos taurus)	SMAD4¹	--	SMAD family member 4	95.05(n) 99.09(a)	540248 NM_001076209.1 NP_001069677.1
rat (Rattus norvegicus)	Smad4¹	--	SMAD family member 4	91.06(n) 98.73(a)	50554 NM_019275.1 NP_062148.1
mouse (Mus musculus)	Smad4^{1, 5}	18 (48.00 cM)⁵	MAD homolog 4 (Drosophila)^{1, 5}	91.53(n)¹ 98.55(a)¹	17128¹ NM_008540.2¹ NP_032566.2¹ AA409925⁵ AB221585⁵ (see all 16)

About this table Species with no ortholog for SMAD4

ENSEMBL Gene Tree for SMAD4

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
About This Section

Paralogs for SMAD4 gene

SMAD6² SMAD7²

(According to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section

10/198 NCBI SNPs in SMAD4 are shown (see all 198 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay) (see all 71)

AB	SNP ID	Valid	Chr 18 pos	Sequence	Recs	AA Chg	Type	More	Recs	Allele freq	Pop	Total sample	More
AB	Genomic Data				Transcription Data				Allele Frequencies
				--	--	--		--	--				--
	rs3819122^1,2	A,C,F,H	46864829(-)	`ATGAAT/GTTCAT`	1	--	ut3¹		4		EU EA WA	418
	rs11663402^1,2	C,F,H	46858846(+)	`TTTACC/TGTTGG`	1	--	ut3¹		4		EU EA WA	420
	rs12456284^1,2	C,F,H	46863966(+)	`TGTTCA/GACCTG`	1	--	ut3¹		18		EA NA EU WA	1656
	rs16952798^1,2	C,F,H	46859520(+)	`ACAAAA/CAAATT`	1	--	ut3¹		7		NA EU EA WA	548
	rs2282544^1,2	A,F,H	46865258(-)	`GTCCCC/GAAAGC`	1	--	ut3¹		5		EA EU WA	1914
	rs1049875^1,2	C,H	46858926(+)	`CTTTTG/CTTCTG`	1	--	ut3¹		10		MN CSAM EA EU WA	1000
--	rs11662245^1,2	A,C	46864382(+)	`CGCGCA/GCACAC`	1	--	ut3¹		0	--	--	--	--
	rs4940037^1,2	F,H	46860701(+)	`TTACAA/GATTCT`	1	--	ut3¹		4		EU EA WA	420
	rs12961857^1,2	C,H	46862595(+)	`TTTTTT/CCCCGT`	1	--	ut3¹		4		EU EA WA	418
	rs12327465^1,2	H	46860845(+)	`TTTTAG/AAATAA`	1	--	ut3¹		4		EU EA WA	420

About this table

HapMap Linkage Disequilibrium images for SMAD4 (up to first 250kb)

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

OMIM: 600993

UniProtKB/Swiss-Prot: SMAD4_HUMAN, Q13485

Defects in SMAD4 are a cause of pancreatic carcinoma [MIM:260350]

Defects in SMAD4 are a cause of juvenile polyposis syndrome (JPS) [MIM:174900]; also known

as juvenile intestinal polyposis (JIP). JPS is an autosomal dominant gastrointestinal

hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal

cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic

spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of

Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here,

polyps tend to occur in the large bowel and are associated with an increased risk of colon and

other gastrointestinal cancers

Defects in SMAD4 are a cause of juvenile polyposis/hereditary hemorrhagic telangiectasia

syndrome (JP/HHT) [MIM:175050]. JP/HHT syndrome phenotype consists of the coexistence of juvenile

polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single

individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping

clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused

by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by

mutations in ENG or ACVRL1. All four genes encode proteins involved in the

transforming-growth-factor-signaling pathway. Although there are reports of patients and families

with phenotypes of both disorders combined, the genetic aetiology of this association is unknown

Defects in SMAD4 may be a cause of colorectal cancer (CRC) [MIM:114500]

10/92 Novoseek disease relationships for SMAD4 gene (see all 92 )

Disease	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
juvenile polyposis syndrome	88.40	12	19014666 (2), 16152648 (1), 17873119 (1), 15378062 (1) (see all 8)
pancreatic cancer	80.93	115	11323508 (3), 12479060 (3), 11783110 (3), 15592526 (3) (see all 60)
polyps juvenile	80.75	2	15447767 (1), 19014666 (1)
pancreatic carcinoma	78.26	95	18985820 (6), 9098646 (5), 12352188 (4), 11866987 (3) (see all 37)
polyposis	77.46	46	10797267 (3), 15031030 (3), 18355998 (3), 12821112 (2) (see all 30)
allelic loss	70.60	31	17088901 (2), 17659731 (2), 19443408 (2), 11337365 (2) (see all 18)
adenocarcinoma	68.63	147	11751510 (6), 11431719 (5), 17587453 (5), 17854080 (5) (see all 57)
pancreatic tumor	67.58	7	16135802 (2), 10415855 (1), 9644295 (1), 11553622 (1) (see all 6)
tumors	64.97	387	15814640 (6), 12352188 (6), 15014009 (5), 10331746 (4) (see all 99)
carcinoma pancreatic ductal	60.11	4	11431719 (1), 11391801 (1), 15084978 (1), 11787853 (1)

About this table

GeneTests: SMAD4

Juvenile Polyposis Syndrome

Human Gene Mutation Database: SMAD4
Genetic Association Database: SMAD4
Human Genome Epidemiology Navigator: SMAD4 (17 documents)

(Possibly Related Articles in Doctor's Guide)
About This Section

Researchers Identify Gene That Causes Juvenile Polyposis

(in PubMed. Associations of this gene to articles via ¹Novoseek, ²HGNC, ³Entrez Gene, ⁴UniProtKB/Swiss-Prot, ⁵UniProtKB/TrEMBL, ⁶GAD, and/or ⁷PharmGKB)
About This Section

10/760 PubMed articles for SMAD4 gene (see all 760 ):

Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. (PubMed id 12417513)^{1, 3, 4, 6} Sayed M.G.... Howe J.R. (2002)
DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. (PubMed id 8553070)^{2, 3, 4} Hahn S.A.... Kern S.E. (1996)
Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. (PubMed id 8774881)^{2, 3, 4} Zhang Y....Derynck R. (1996)
The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. (PubMed id 15235019)^{1, 3, 6} Howe J.R....Lynch H.T. (2004)
Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. (PubMed id 9811934)^{1, 3, 4} Houlston R.... Tomlinson I. (1998)
Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation. (PubMed id 11818334)^{1, 3, 4} Wan M.... Cao X. (2002)
A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). (PubMed id 15031030)^{1, 3, 4} Gallione C.J.... Marchuk D.A. (2004)
Genomic sequencing of DPC4 in the analysis of familial pancreatic carcinoma. (PubMed id 9098646)^{1, 3, 4} Moskaluk C.A....Kern S.E. (1997)
Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes. (PubMed id 9389648)^{1, 3, 4} Liu F.... Massague J. (1997)
LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density. (PubMed id 14727154)^{1, 3, 6} Mizuguchi T.... Yoshiura K. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
About This Section

Entrez Gene: 4089	HGNC: 6770	AceView: SMAD4andELAC1	Ensembl:ENSG00000141646	euGenes: HUgn4089
ECgene: SMAD4	H-InvDB: SMAD4

(According to HUGE)
About This Section

(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
ATLAS Chromosomes in Cancer entry for SMAD4	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.genetests.org/query?gene=SMAD4

Licensable Technologies for SMAD4
(Available from WIS Yeda, Salk, Tufts)

About This Section

(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
Sigma-Aldrich, R&D Systems, Millipore, Abnova, and/or Invitrogen, Clones available from OriGene,and/or Invitrogen, Drugs and/or compounds by Sigma-Aldrich,
Enzo Life Sciences, and/or Tocris Bioscience)
About This Section

Products for SMAD4:

TaqMan ® Gene Expression Assays

TaqMan ® Genotyping Assays

Free SNP selection tool

Invitrogen iPath Pathways	Invitrogen BLOCK-iT™ RNAi
Invitrogen Antibodies	Invitrogen Assays
Invitrogen Clones	Invitrogen Q-PCR Products
Invitrogen Human Recombinant Kinases	Invitrogen Custom Antibody and Peptide Service
Invitrogen Proteins / Assays / Screening Services	Search Invitrogen catalog for SMAD4-related products

	Millipore Custom Antibody & Bulk Services
	Millipore Preclinical / Clinical Development Services
	Millipore Immunoassay Services
	Millipore Target Screening & Profiling Services

	Predesigned and custom siRNAs for SMAD4		Antibodies for SMAD4
	Explore super-pooled esiRNAs		Proteins for SMAD4
	Lentivirus-delivered shRNAs for SMAD4		Browse small molecules at Sigma-Aldrich
	"Your Favorite Gene" Pathways		feedback

	Antibodies		Primer Pairs
	Cell Culture Products		ELISAs
	Flow Cytometry Kits		Protease Activity Assays & Reagents
	Cell Selection/Detection Kits & Reagents		ELISA/Assay Development Kits & Reagents
	Multiplex/Array Assay Kits & Reagents		ELISpot Kits & Development Modules
	Recombinant & Natural Proteins

	Recombinant Proteins (SMAD4)
	Antibodies (SMAD4)
	Chimera RNAi (SMAD4)
	Custom Service for Mouse Mab
	Custom Service for Rabbit Pab from Full-length Protein

Antibodies & Assays for SMAD4

	Recombinant Proteins (Smad4)
	Antibodies (Smad4)

	Tagged/untagged cDNA clones
	Validated SYBR primer pairs
	Purified proteins from HEK293T cells
	Western blot validated antibodies
	shRNA in GFP-retroviral vector

Search Tocris compounds for SMAD4

Search www.enzolifesicences.com for proteins, assays, substrates, inhibitors & antibodies

Antibodies for SMAD4

GeneCards Homepage - Last full update: 2 Jul 2009 Incremental update: 13 Oct 2009

Random Gene From GIFtS :

about GIFtS

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Developed at the Crown Human Genome Center & Weizmann Institute of Science

The GeneCards Human Gene Database: Copyright © 1996-2009, Weizmann Institute of Science. All Rights Reserved.
SMAD4 Gene at Home site.
Version 2.41.1
server4.xennexinc.com

SMAD4 Gene

protein-coding GIFtS: 71

Aliases &
Descriptions
for SMAD4

Summaries
for SMAD4

Genomic Location
for SMAD4

Proteins
for SMAD4

Protein Domains/
Families
for SMAD4

Gene Function
for SMAD4

Pathways & Interactions
for SMAD4

Drugs & Compounds
for SMAD4

Transcripts
for SMAD4

Expression
for SMAD4

Orthologs
for SMAD4

Paralogs
for SMAD4

SNPs/Variants
for SMAD4

Disorders & Mutations
for SMAD4

Medical News
for SMAD4

Publications
for SMAD4

Search for SMAD4

Genome Databases showing SMAD4

Other Databases showing SMAD4

Specialized Databases showing SMAD4

Licensable Technologies
for SMAD4

Services
for SMAD4

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

SMAD4 Gene

protein-coding GIFtS: 71

Aliases & Descriptionsfor SMAD4

Summariesfor SMAD4

Genomic Locationfor SMAD4

Proteinsfor SMAD4

Protein Domains/Familiesfor SMAD4

Gene Functionfor SMAD4

Pathways & Interactionsfor SMAD4

Drugs & Compoundsfor SMAD4

Transcriptsfor SMAD4

Expression for SMAD4

Orthologsfor SMAD4

Paralogsfor SMAD4

SNPs/Variantsfor SMAD4

Disorders & Mutationsfor SMAD4

Medical Newsfor SMAD4

Publicationsfor SMAD4

Search for SMAD4

Genome Databases showing SMAD4

Other Databases showing SMAD4

Specialized Databases showing SMAD4

Licensable Technologiesfor SMAD4

Servicesfor SMAD4

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Aliases &
Descriptions
for SMAD4

Summaries
for SMAD4

Genomic Location
for SMAD4

Proteins
for SMAD4

Protein Domains/
Families
for SMAD4

Gene Function
for SMAD4

Pathways & Interactions
for SMAD4

Drugs & Compounds
for SMAD4

Transcripts
for SMAD4

Expression
for SMAD4

Orthologs
for SMAD4

Paralogs
for SMAD4

SNPs/Variants
for SMAD4

Disorders & Mutations
for SMAD4

Medical News
for SMAD4

Publications
for SMAD4

Licensable Technologies
for SMAD4

Services
for SMAD4