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FLASH GENE

Symbol

SMAD5

contributors: mct/npt - updated : 28-08-2013

HGNC name	SMAD family member 5
HGNC id	6771

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	49.89 kb     8 Exon(s)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - IL9 - SMAD5 - D5S393 - D5S89 - D5S399 - SPOCK1 /D5S429 - D5S479 - D5S1983 /HNRNPA0 - D5S414 - CDC25C - BRD8 /D5S2603 - D5S1701 - D5S500 - HSPA9 /D5S2430 - EGR1 - D5S476 - D5S1856 - CTNNA1 - qter
Authors	Zavadil (97), Horrigan (99)

RNA

TRANSCRIPTS	type	messenger

text	an antisense transcript DAMS only expressed in fetal tissues and pancreatic tumor all variants (1-3) encode the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005903 8 - 7012 NP_005894 52.13 465 - Gemma (1998) NM_001001419 9 - 7096 NP_001001419 52.13 465 - Gemma (1998) NM_001001420 7 - 6937 NP_001001420 52.13 465 - Gemma (1998)

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear inner     highly

cell lineage

cell lines

fluid/secretion

at STAGE

Text	ubiquitous during testis development but becomes cell-specific in the adult (Itman 2008)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	Dwarfin (DWA)/MH1 DNA binding domain including a nuclear localization-like signal (NLS-L)
	a double loop region, followed by a linker region
	a DWB/MH2 heterodimerization and transactivation domain

mono polymer

heteromer , trimer , complex

HOMOLOGY

interspecies

homolog to Drosophila Mad (mothers against dpp) gene JV5-1

Homologene

FAMILY

dwarfin/SMAD family

CATEGORY

regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,nucleus
text	translocating to nucleus after binding to MADH4
	cytoplasmic in the absence of ligand,translocated to nucleus when complexed with MADH4
	mitochondrial in chondrogenic cell lines

basic FUNCTION	intracellular mediator of TGFB family of cytokines
	BMP4/SMAD5 dependent stress erythropoiesis is required for the expansion of erythroid progenitors during fetal development (Porayette 2008)

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

transducer of TGFB and of bone morphogenetic proteins signaling

a component

heterotrimerizing with MADH4

INTERACTION

DNA

RNA

small molecule

protein	RUNX2 (PEBP2A) and SMURF1
	interacting with activin receptor
	ADP-ribosylation of SMAD proteins by PARP1 is a key step in controlling the strength and duration of SMAD-mediated transcription
	binds to SMAD1, SMAD5 and SMAD9, and represses bone morphogenetic protein (BMP) signaling responses
	CREBZF inhibits the function of BMP6 by interacting with SMAD1, SMAD5, SMAD9
	PLEKHO1 is an activator of the SMURF1 ubiquitin ligase acting to promote the ubiquitylation of SMAD5 and MAP2K1

cell & other

REGULATION

activated by

BMPR1A (serotonin transactivates BMPR1A, to activate SMAD 1/5/8 via Rho and Rho kinase in pulmonary artery smooth muscle cells; Rho and Rho kinase also participate in the activation of Smads by BMP) (Liu 2009)

Other

undergoing phosphorylation

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   LOH     in leukemia constitutional       loss of function deficiency in the SMAD5-mediated signaling resulted in apoptosis of hair cells, suggesting SMAD5 is a gene that may be related with presbycusis (Yang 2009)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

lack of Madh5,(Smad5) expression in mice results in bilateral Nodal expression in lateral plate mesoderm (LPM),embryonic lethality no turning