P97454 (SMAD5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mothers against decapentaplegic homolog 5
Short name=MAD homolog 5
Short name=Mothers against DPP homolog 5

Alternative name(s):
Dwarfin-C
Short name=Dwf-C
SMAD family member 5
Short name=SMAD 5
Short name=Smad5
Short name=mSmad5

Gene names

Name:	Smad5
Synonyms:	Madh5, Msmad5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD) By similarity. Required for angiogenesis.
Subunit structure	May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3 By similarity. Interacts with WWP1. Ref.7
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with SMAD4 By similarity.
Post-translational modification	Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase. Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1 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	Angiogenesis Differentiation Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Developmental protein
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from genetic interaction PubMed 20843790. Source: BHF-UCL Mullerian duct regression Inferred from electronic annotation. Source: Compara angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW bone development Inferred from genetic interaction PubMed 19224984. Source: MGI cardiac muscle contraction Inferred from mutant phenotype PubMed 17456754. Source: MGI cartilage development Inferred from genetic interaction PubMed 19224984. Source: MGI cellular response to BMP stimulus Inferred from genetic interaction PubMed 20843790. Source: BHF-UCL cellular response to organic cyclic compound Inferred from direct assay PubMed 19103752. Source: MGI embryonic pattern specification Inferred from sequence or structural similarity. Source: UniProtKB erythrocyte differentiation Inferred from mutant phenotype PubMed 15591122. Source: MGI germ cell development Inferred from mutant phenotype PubMed 11404080. Source: MGI osteoblast fate commitment Inferred from genetic interaction PubMed 15150273. Source: MGI positive regulation of osteoblast differentiation Inferred from genetic interaction PubMed 15150273. Source: MGI positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Inferred from genetic interaction PubMed 20843790. Source: BHF-UCL protein phosphorylation Inferred from direct assay PubMed 18776146. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 11376112. Source: MGI ureteric bud development Inferred from expression pattern PubMed 14656760. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay PubMed 19103752. Source: MGI nucleus Inferred from direct assay PubMed 12151307. Source: UniProtKB transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular_function	RNA polymerase II core promoter sequence-specific DNA binding Inferred from direct assay PubMed 18692037. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
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 – 465	464	Mothers against decapentaplegic homolog 5		PRO_0000090866
Regions
	Domain	13 – 137	125	MH1
	Domain	271 – 465	195	MH2
	Compositional bias	40 – 46	7	Poly-Lys
Sites
	Metal binding	65	1	Zinc By similarity
	Metal binding	110	1	Zinc By similarity
	Metal binding	122	1	Zinc By similarity
	Metal binding	127	1	Zinc By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylthreonine By similarity
	Modified residue	133	1	Phosphoserine By similarity
	Modified residue	462	1	Phosphoserine By similarity
	Modified residue	463	1	Phosphoserine By similarity
	Modified residue	465	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	196	1	S → P in AAB39737. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P97454 [UniParc]. Last modified May 4, 2001. Version 2. Checksum: D66B638DA76BC20B	FASTA	465	52,172
	10 20 30 40 50 60 MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG 70 80 90 100 110 120 QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE 130 140 150 160 170 180 VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP 190 200 210 220 230 240 NNAPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMAPDNSQP 250 260 270 280 290 300 MDTSSNMIPQ TMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT 310 320 330 340 350 360 DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC 370 380 390 400 410 420 NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW 430 440 450 460 GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth." Yingling J.M., Das P., Savage C., Zhang M., Padgett R.W., Wang X.-F. Proc. Natl. Acad. Sci. U.S.A. 93:8940-8944(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The C-terminal domain of Mad-like signal transducers is sufficient for biological activity in the Xenopus embryo and transcriptional activation." Meersseman G., Verschueren K., Nelles L., Blumenstock C., Kraft H., Wuytens G., Remacle J., Kozak C.A., Tylzanowski P., Niehrs C., Huylebroeck D. Mech. Dev. 61:127-140(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Genomic organization and expression of mouse Smad5." Chang H., Kraft H., Verschueren K., Wang P., Huylebroeck D., Matzuk M.M. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: 129/Sv.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Spinal cord.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[6]	"Functions of mammalian Smad genes as revealed by targeted gene disruption in mice." Weinstein M., Yang X., Deng C.-X. Cytokine Growth Factor Rev. 11:49-58(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[7]	"Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1)." Komuro A., Imamura T., Saitoh M., Yoshida Y., Yamori T., Miyazono K., Miyazawa K. Oncogene 23:6914-6923(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH WWP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U58993 mRNA. Translation: AAB07871.1. U77638 mRNA. Translation: AAB39737.1. AF063006 mRNA. Translation: AAC83580.1. AK082997 mRNA. Translation: BAC38724.1. BC050001 mRNA. Translation: AAH50001.2.
IPI	IPI00125470.
RefSeq	NP_001157513.1. NM_001164041.1. NP_001157514.1. NM_001164042.1. NP_032567.1. NM_008541.3.
UniGene	Mm.272920.
3D structure databases
ProteinModelPortal	P97454.
SMR	P97454. Positions 10-133, 270-453.
ModBase	Search...
PTM databases
PhosphoSite	P97454.
Proteomic databases
PaxDb	P97454.
PRIDE	P97454.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000069557; ENSMUSP00000065798; ENSMUSG00000021540. ENSMUST00000109874; ENSMUSP00000105500; ENSMUSG00000021540. ENSMUST00000109876; ENSMUSP00000105502; ENSMUSG00000021540.
GeneID	17129.
KEGG	mmu:17129.
Organism-specific databases
CTD	4090.
MGI	MGI:1328787. Smad5.
Phylogenomic databases
eggNOG	NOG330956.
GeneTree	ENSGT00600000084186.
HOGENOM	HOG000286018.
HOVERGEN	HBG053353.
InParanoid	P97454.
KO	K16790.
OMA	NRVGEAY.
OrthoDB	EOG4HDSTH.
Gene expression databases
Bgee	P97454.
CleanEx	MM_SMAD5.
Genevestigator	P97454.
GermOnline	ENSMUSG00000021540. Mus musculus.
Family and domain databases
Gene3D	2.60.200.10. 1 hit. 3.90.520.10. 1 hit.
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. [Graphical view]
PANTHER	PTHR13703. PTHR13703. 1 hit.
Pfam	PF03165. MH1. 1 hit. PF03166. MH2. 1 hit. [Graphical view]
SMART	SM00523. DWA. 1 hit. SM00524. DWB. 1 hit. [Graphical view]
SUPFAM	SSF56366. MAD_MH1. 1 hit. SSF49879. SMAD_FHA. 1 hit.
PROSITE	PS51075. MH1. 1 hit. PS51076. MH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	291320.
SOURCE	Search...

Entry information

Entry name

SMAD5_MOUSE

Accession

Primary (citable) accession number: P97454
Secondary accession number(s): P70341, Q810K0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 4, 2001
Last sequence update:	May 4, 2001
Last modified:	April 3, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program