Reactome | UniProt:Q99717 SMAD5

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UniProt:Q99717 SMAD5 Show undefined attributes

chain	initiator methionine:1 chain:2-465
checksum	4A1FD7EC7BD06728
comment	FUNCTION Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form a heteromeric complex which translocates into the nucleus acting as transcription factor (PubMed:9442019). In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network (PubMed:33510867). Non-phosphorylated SMAD5 has a cytoplasmic role in energy metabolism regulation by promoting mitochondrial respiration and glycolysis in response to cytoplasmic pH changes (PubMed:28675158). Mechanistically, interacts with hexokinase 1/HK1 and thereby accelerates glycolysis (PubMed:28675158).SUBUNIT Homodimer (PubMed:33510867). Forms trimers with the co-SMAD SMAD4 (PubMed:9442019). Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1. Interacts with TMEM119 (By similarity). Interacts with ZNF8 (PubMed:12370310). Interacts with RANBP3L (PubMed:25755279). Interacts with HK1 (PubMed:28675158). Interacts with HGS; this interaction attenuates BMP signaling (PubMed:16516194).INTERACTION Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.TISSUE SPECIFICITY Ubiquitous.PTM Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.PTM Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.SIMILARITY Belongs to the dwarfin/SMAD family.
crossReference	[DatabaseIdentifier:11445478] ENSEMBL:ENSG00000113658 [DatabaseIdentifier:11532363] ENSEMBL:ENSP00000426696 [DatabaseIdentifier:11532362] ENSEMBL:ENSP00000441954 [DatabaseIdentifier:11532361] ENSEMBL:ENSP00000446474 [DatabaseIdentifier:11655062] ENSEMBL:ENST00000545620 [DatabaseIdentifier:11655060] ENSEMBL:ENST00000509297 [DatabaseIdentifier:11655061] ENSEMBL:ENST00000545279 [DatabaseIdentifier:11784066] GeneCards:SMAD5 [DatabaseIdentifier:11799593] GlyGen:Q99717 [DatabaseIdentifier:11837169] HPA:ENSG00000113658-SMAD5 [DatabaseIdentifier:12121657] OpenTargets:ENSG00000113658 [DatabaseIdentifier:12155285] PDB:6TCE [DatabaseIdentifier:12155284] PDB:6FZS [DatabaseIdentifier:12239621] PRO:Q99717 [DatabaseIdentifier:12281982] Pharos - Targets:Q99717 [DatabaseIdentifier:12311296] RefSeq:XP_024301814.1 [DatabaseIdentifier:12311298] RefSeq:NP_005894.3 [DatabaseIdentifier:12311295] RefSeq:NP_001001419.1 [DatabaseIdentifier:12311299] RefSeq:XP_016864959.1 [DatabaseIdentifier:12311292] RefSeq:XP_054208561.1 [DatabaseIdentifier:12311294] RefSeq:XP_054208562.1 [DatabaseIdentifier:12311293] RefSeq:XP_054208560.1 [DatabaseIdentifier:12311300] RefSeq:NP_001001420.1 [DatabaseIdentifier:12311297] RefSeq:XP_024301815.1
databaseName	UniProt
dbId	64630
description	recommendedName: fullName evidence="17"SMAD family member 5 shortName evidence="16"SMAD 5 shortName: hSmad5 alternativeName: JV5-1 alternativeName: Mothers against decapentaplegic homolog 5 shortName: MAD homolog 5 shortName: Mothers against DPP homolog 5
displayName	UniProt:Q99717 SMAD5
geneName	SMAD5 MADH5
identifier	Q99717
isSequenceChanged	false
keyword	3D-structure Acetylation Cytoplasm Direct protein sequencing DNA-binding Metal-binding Mitochondrion Nucleus Phosphoprotein Proteomics identification Reference proteome Transcription Transcription regulation Zinc
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	SMAD5
otherIdentifier	1013_at 11729717_a_at 11729718_s_at 11729719_a_at 11741023_a_at 11757679_s_at 16989534 16989544 1952_s_at 205187_PM_at 205187_at 205188_PM_s_at 205188_s_at 225219_PM_at 225219_at 225223_PM_at 225223_at 235451_PM_at 235451_at 2830018 2830019 2830020 2830021 2830022 2830023 2830024 2830027 2830028 2830029 2830030 2830031 2830032 2830033 2830037 2830039 2830041 2830042 2830043 2830046 2830047 2830048 2830049 2830050 2830051 39926_at 4090 54698_at 8108238 84185_r_at A_14_P106211 A_14_P121517 A_14_P123776 A_14_P137757 A_19_P00804893 A_21_P0004302 A_23_P144944 A_33_P3220445 GE55680 GE79186 GO:0000122 GO:0000785 GO:0000977 GO:0000978 GO:0000981 GO:0001227 GO:0001503 GO:0001649 GO:0001657 GO:0001673 GO:0001880 GO:0002051 GO:0003012 GO:0003161 GO:0003677 GO:0003700 GO:0005515 GO:0005634 GO:0005654 GO:0005667 GO:0005737 GO:0005739 GO:0005829 GO:0006355 GO:0006357 GO:0006879 GO:0007165 GO:0007179 GO:0007281 GO:0009653 GO:0009880 GO:0010468 GO:0010629 GO:0017151 GO:0022414 GO:0030154 GO:0030218 GO:0030509 GO:0031625 GO:0032502 GO:0032991 GO:0043066 GO:0045669 GO:0045893 GO:0045944 GO:0046872 GO:0048856 GO:0048863 GO:0051216 GO:0060048 GO:0060348 GO:0060395 GO:0070411 GO:0071141 GO:0071144 GO:0071363 GO:0141091 GO:1902045 GO:1990262 GO:1990837 HMNXSV003001187 HMNXSV003024162 Hs.165210.0.A1_3p_at Hs.167700.0.S1_3p_at Hs.167700.0.S2_3p_at ILMN_1674551 ILMN_1761994 ILMN_2371984 PH_hs_0022793 TC05000683.hg TC05002640.hg U59913_at g2317785_3p_at g5174514_3p_a_at p23065
physicalEntity	[EntityWithAccessionedSequence:R-HSA-201431] SMAD5 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-201473] p-S463,S465-SMAD5 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-201432] p-S463,S465-SMAD5 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000113658] ENSEMBL:ENSG00000113658 SMAD5 [ReferenceDNASequence:12722307] UCSC:Q99717 SMAD5 [ReferenceDNASequence:11311152] BioGPS Gene:4090 SMAD5 [ReferenceDNASequence:11397409] COSMIC - genes:SMAD5 SMAD5 [ReferenceDNASequence:11407892] CTD Gene:4090 SMAD5 [ReferenceDNASequence:11434091] dbSNP Gene:4090 SMAD5 [ReferenceDNASequence:11815690] HGNC:6771 SMAD5 [ReferenceDNASequence:11854824] KEGG:hsa:4090 SMAD5 [ReferenceDNASequence:11940941] Monarch:4090 SMAD5 [ReferenceDNASequence:12025034] NCBI Gene:4090 SMAD5 [ReferenceDNASequence:12107331] OMIM:603110 SMAD5
referenceTranscript	[ReferenceRNASequence:12493379] RefSeq:NM_005903.6 SMAD5 [ReferenceRNASequence:12493380] RefSeq:XM_054352586.1 SMAD5 [ReferenceRNASequence:12493378] RefSeq:XM_054352585.1 SMAD5 [ReferenceRNASequence:12493384] RefSeq:XM_024446047.2 SMAD5 [ReferenceRNASequence:12493383] RefSeq:XM_024446046.2 SMAD5 [ReferenceRNASequence:12493382] RefSeq:NM_001001419.3 SMAD5 [ReferenceRNASequence:12493381] RefSeq:NM_001001420.3 SMAD5 [ReferenceRNASequence:12493377] RefSeq:XM_017009470.3 SMAD5 [ReferenceRNASequence:12493376] RefSeq:XM_054352587.1 SMAD5
schemaClass	ReferenceGeneProduct
secondaryIdentifier	SMAD5_HUMAN O14688 Q15798 Q9UQA1
sequenceLength	465
species	[Species:48887] Homo sapiens
stId	uniprot:Q99717
url	http://purl.uniprot.org/uniprot/Q99717

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-201431] SMAD5 [cytosol] [EntityWithAccessionedSequence:R-HSA-201473] p-S463,S465-SMAD5 [cytosol] [EntityWithAccessionedSequence:R-HSA-201432] p-S463,S465-SMAD5 [nucleoplasm]
(referenceSequence)	[ModifiedResidue:201440] O-phospho-L-serine at 463 [ModifiedResidue:201469] O-phospho-L-serine at 465
(interactor)	[UndirectedInteraction:11145593] UniProt:Q9H8X2 <-> UniProt:Q99717 (IntAct) [UndirectedInteraction:11249429] UniProt:Q9HAU4 <-> UniProt:Q99717 (IntAct) [UndirectedInteraction:11283661] UniProt:P17844 <-> UniProt:Q99717 (IntAct)