UniProtKB - Q99717 (SMAD5_HUMAN)
Protein
Mothers against decapentaplegic homolog 5
Gene
SMAD5
Organism
Homo sapiens (Human)
Status
Functioni
Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 65 | ZincBy similarity | 1 | |
Metal bindingi | 110 | ZincBy similarity | 1 | |
Metal bindingi | 122 | ZincBy similarity | 1 | |
Metal bindingi | 127 | ZincBy similarity | 1 |
GO - Molecular functioni
- DEAD/H-box RNA helicase binding Source: BHF-UCL
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: Ensembl
- I-SMAD binding Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: BHF-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription factor binding Source: GO_Central
- ubiquitin protein ligase binding Source: BHF-UCL
GO - Biological processi
- anatomical structure morphogenesis Source: GO_Central
- BMP signaling pathway Source: UniProtKB
- bone development Source: Ensembl
- cardiac muscle contraction Source: Ensembl
- cartilage development Source: Ensembl
- cell differentiation Source: GO_Central
- cellular response to organic cyclic compound Source: Ensembl
- embryonic pattern specification Source: UniProtKB
- erythrocyte differentiation Source: Ensembl
- germ cell development Source: Ensembl
- Mullerian duct regression Source: Ensembl
- osteoblast fate commitment Source: Ensembl
- positive regulation of osteoblast differentiation Source: Ensembl
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: GO_Central
- positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
- protein phosphorylation Source: Ensembl
- signal transduction Source: UniProtKB
- SMAD protein signal transduction Source: BHF-UCL
- transforming growth factor beta receptor signaling pathway Source: GO_Central
- ureteric bud development Source: Ensembl
Keywordsi
Molecular function | DNA-binding |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q99717 |
Reactomei | R-HSA-201451, Signaling by BMP |
SignaLinki | Q99717 |
SIGNORi | Q99717 |
Names & Taxonomyi
Protein namesi | Recommended name: Mothers against decapentaplegic homolog 5Short name: MAD homolog 5 Short name: Mothers against DPP homolog 5 Alternative name(s): JV5-1 SMAD family member 5 Short name: SMAD 5 Short name: Smad5 Short name: hSmad5 |
Gene namesi | Name:SMAD5 Synonyms:MADH5 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000113658.16 |
HGNCi | HGNC:6771, SMAD5 |
MIMi | 603110, gene |
neXtProti | NX_Q99717 |
Subcellular locationi
Cytosol
- cytosol Source: HPA
Nucleus
- heteromeric SMAD protein complex Source: GO_Central
- nuclear chromatin Source: NTNU_SB
- nucleoplasm Source: HPA
- nucleus Source: BHF-UCL
Other locations
- cytoplasm Source: BHF-UCL
- protein-containing complex Source: MGI
- SMAD protein complex Source: BHF-UCL
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 419 | G → S: Loss of phosphorylation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 4090 |
OpenTargetsi | ENSG00000113658 |
PharmGKBi | PA30528 |
Miscellaneous databases
Pharosi | Q99717, Tbio |
Polymorphism and mutation databases
BioMutai | SMAD5 |
DMDMi | 13959566 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources1 Publication | |||
ChainiPRO_0000090865 | 2 – 465 | Mothers against decapentaplegic homolog 5Add BLAST | 464 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylthreonineCombined sources1 Publication | 1 | |
Modified residuei | 463 | PhosphoserineCombined sources | 1 | |
Modified residuei | 465 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.
Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q99717 |
jPOSTi | Q99717 |
MassIVEi | Q99717 |
MaxQBi | Q99717 |
PaxDbi | Q99717 |
PeptideAtlasi | Q99717 |
PRIDEi | Q99717 |
ProteomicsDBi | 78432 |
PTM databases
iPTMneti | Q99717 |
PhosphoSitePlusi | Q99717 |
Expressioni
Tissue specificityi
Ubiquitous.
Gene expression databases
Bgeei | ENSG00000113658, Expressed in female gonad and 242 other tissues |
ExpressionAtlasi | Q99717, baseline and differential |
Genevisiblei | Q99717, HS |
Organism-specific databases
HPAi | ENSG00000113658, Low tissue specificity |
Interactioni
Subunit structurei
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.
Interacts with WWP1.
Interacts with TMEM119 (By similarity).
Interacts with ZNF8 (PubMed:12370310).
Interacts with RANBP3L (PubMed:25755279).
By similarity4 PublicationsBinary interactionsi
Hide detailsQ99717
With | #Exp. | IntAct |
---|---|---|
DDX5 [P17844] | 3 | EBI-6391136,EBI-351962 |
POU6F2 [P78424] | 3 | EBI-6391136,EBI-12029004 |
WBP2 [Q969T9] | 3 | EBI-6391136,EBI-727055 |
GO - Molecular functioni
- DEAD/H-box RNA helicase binding Source: BHF-UCL
- I-SMAD binding Source: GO_Central
- transcription factor binding Source: GO_Central
- ubiquitin protein ligase binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 110265, 66 interactors |
DIPi | DIP-57571N |
IntActi | Q99717, 37 interactors |
MINTi | Q99717 |
STRINGi | 9606.ENSP00000441954 |
Miscellaneous databases
RNActi | Q99717, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SASBDBi | Q99717 |
SMRi | Q99717 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 13 – 137 | MH1PROSITE-ProRule annotationAdd BLAST | 125 | |
Domaini | 271 – 465 | MH2PROSITE-ProRule annotationAdd BLAST | 195 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 40 – 46 | Poly-Lys | 7 |
Sequence similaritiesi
Belongs to the dwarfin/SMAD family.Curated
Phylogenomic databases
eggNOGi | KOG3701, Eukaryota |
GeneTreei | ENSGT00940000155437 |
HOGENOMi | CLU_026736_0_2_1 |
InParanoidi | Q99717 |
OMAi | MPRGDVQ |
OrthoDBi | 608001at2759 |
PhylomeDBi | Q99717 |
Family and domain databases
Gene3Di | 2.60.200.10, 1 hit 3.90.520.10, 1 hit |
InterProi | View protein in InterPro IPR013790, Dwarfin IPR003619, MAD_homology1_Dwarfin-type IPR013019, MAD_homology_MH1 IPR017855, SMAD-like_dom_sf IPR001132, SMAD_dom_Dwarfin-type IPR008984, SMAD_FHA_dom_sf IPR036578, SMAD_MH1_sf |
PANTHERi | PTHR13703, PTHR13703, 1 hit |
Pfami | View protein in Pfam PF03165, MH1, 1 hit PF03166, MH2, 1 hit |
SMARTi | View protein in SMART SM00523, DWA, 1 hit SM00524, DWB, 1 hit |
SUPFAMi | SSF49879, SSF49879, 1 hit SSF56366, SSF56366, 1 hit |
PROSITEi | View protein in PROSITE PS51075, MH1, 1 hit PS51076, MH2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
Q99717-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME
60 70 80 90 100
ELEKALSSPG QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS
110 120 130 140 150
HHELKPLDIC EFPFGSKQKE VCINPYHYKR VESPVLPPVL VPRHNEFNPQ
160 170 180 190 200
HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP NNTPFPLSPN SPYPPSPASS
210 220 230 240 250
TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP MDTSNNMIPQ
260 270 280 290 300
IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT
310 320 330 340 350
DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD
360 370 380 390 400
SSIFVQSRNC NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF
410 420 430 440 450
EAVYELTKMC TIRMSFVKGW GAEYHRQDVT STPCWIEIHL HGPLQWLDKV
460
LTQMGSPLNP ISSVS
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YAK7 | H0YAK7_HUMAN | Mothers against decapentaplegic hom... | SMAD5 | 174 | Annotation score: | ||
D6RBB4 | D6RBB4_HUMAN | Mothers against decapentaplegic hom... | SMAD5 | 134 | Annotation score: | ||
D6RIZ9 | D6RIZ9_HUMAN | Mothers against decapentaplegic hom... | SMAD5 | 128 | Annotation score: | ||
D6R9D4 | D6R9D4_HUMAN | Mothers against decapentaplegic hom... | SMAD5 | 80 | Annotation score: | ||
H0YAM3 | H0YAM3_HUMAN | Mothers against decapentaplegic hom... | SMAD5 | 60 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 175 | D → H in AAC50791 (PubMed:8673135).Curated | 1 | |
Sequence conflicti | 237 | N → P in AAC50791 (PubMed:8673135).Curated | 1 | |
Sequence conflicti | 293 | S → R in AAC50791 (PubMed:8673135).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U59913 mRNA Translation: AAC50791.1 AF010601 mRNA Translation: AAB66353.1 AF010607 , AF010602, AF010603, AF010604, AF010605, AF010606 Genomic DNA Translation: AAB92396.1 U73825 mRNA Translation: AAB95090.1 AF009744 , AF009739, AF009740, AF009741, AF009742, AF009743 Genomic DNA Translation: AAB82655.1 AF009678 mRNA Translation: AAB72180.1 BC009682 mRNA Translation: AAH09682.1 |
CCDSi | CCDS75308.1 |
RefSeqi | NP_001001419.1, NM_001001419.2 NP_001001420.1, NM_001001420.2 NP_005894.3, NM_005903.6 XP_016864959.1, XM_017009470.1 |
Genome annotation databases
Ensembli | ENST00000509297; ENSP00000426696; ENSG00000113658 ENST00000545279; ENSP00000441954; ENSG00000113658 ENST00000545620; ENSP00000446474; ENSG00000113658 |
GeneIDi | 4090 |
KEGGi | hsa:4090 |
UCSCi | uc032vlw.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U59913 mRNA Translation: AAC50791.1 AF010601 mRNA Translation: AAB66353.1 AF010607 , AF010602, AF010603, AF010604, AF010605, AF010606 Genomic DNA Translation: AAB92396.1 U73825 mRNA Translation: AAB95090.1 AF009744 , AF009739, AF009740, AF009741, AF009742, AF009743 Genomic DNA Translation: AAB82655.1 AF009678 mRNA Translation: AAB72180.1 BC009682 mRNA Translation: AAH09682.1 |
CCDSi | CCDS75308.1 |
RefSeqi | NP_001001419.1, NM_001001419.2 NP_001001420.1, NM_001001420.2 NP_005894.3, NM_005903.6 XP_016864959.1, XM_017009470.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6FZS | X-ray | 2.31 | A/B | 9-138 | [»] | |
6TCE | X-ray | 2.92 | A | 9-138 | [»] | |
SASBDBi | Q99717 | |||||
SMRi | Q99717 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110265, 66 interactors |
DIPi | DIP-57571N |
IntActi | Q99717, 37 interactors |
MINTi | Q99717 |
STRINGi | 9606.ENSP00000441954 |
PTM databases
iPTMneti | Q99717 |
PhosphoSitePlusi | Q99717 |
Polymorphism and mutation databases
BioMutai | SMAD5 |
DMDMi | 13959566 |
Proteomic databases
EPDi | Q99717 |
jPOSTi | Q99717 |
MassIVEi | Q99717 |
MaxQBi | Q99717 |
PaxDbi | Q99717 |
PeptideAtlasi | Q99717 |
PRIDEi | Q99717 |
ProteomicsDBi | 78432 |
Protocols and materials databases
Antibodypediai | 7303, 566 antibodies |
DNASUi | 4090 |
Genome annotation databases
Ensembli | ENST00000509297; ENSP00000426696; ENSG00000113658 ENST00000545279; ENSP00000441954; ENSG00000113658 ENST00000545620; ENSP00000446474; ENSG00000113658 |
GeneIDi | 4090 |
KEGGi | hsa:4090 |
UCSCi | uc032vlw.2, human |
Organism-specific databases
CTDi | 4090 |
DisGeNETi | 4090 |
EuPathDBi | HostDB:ENSG00000113658.16 |
GeneCardsi | SMAD5 |
HGNCi | HGNC:6771, SMAD5 |
HPAi | ENSG00000113658, Low tissue specificity |
MIMi | 603110, gene |
neXtProti | NX_Q99717 |
OpenTargetsi | ENSG00000113658 |
PharmGKBi | PA30528 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3701, Eukaryota |
GeneTreei | ENSGT00940000155437 |
HOGENOMi | CLU_026736_0_2_1 |
InParanoidi | Q99717 |
OMAi | MPRGDVQ |
OrthoDBi | 608001at2759 |
PhylomeDBi | Q99717 |
Enzyme and pathway databases
PathwayCommonsi | Q99717 |
Reactomei | R-HSA-201451, Signaling by BMP |
SignaLinki | Q99717 |
SIGNORi | Q99717 |
Miscellaneous databases
BioGRID-ORCSi | 4090, 5 hits in 121 CRISPR screens |
ChiTaRSi | SMAD5, human |
GeneWikii | Mothers_against_decapentaplegic_homolog_5 |
GenomeRNAii | 4090 |
Pharosi | Q99717, Tbio |
PROi | PR:Q99717 |
RNActi | Q99717, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000113658, Expressed in female gonad and 242 other tissues |
ExpressionAtlasi | Q99717, baseline and differential |
Genevisiblei | Q99717, HS |
Family and domain databases
Gene3Di | 2.60.200.10, 1 hit 3.90.520.10, 1 hit |
InterProi | View protein in InterPro IPR013790, Dwarfin IPR003619, MAD_homology1_Dwarfin-type IPR013019, MAD_homology_MH1 IPR017855, SMAD-like_dom_sf IPR001132, SMAD_dom_Dwarfin-type IPR008984, SMAD_FHA_dom_sf IPR036578, SMAD_MH1_sf |
PANTHERi | PTHR13703, PTHR13703, 1 hit |
Pfami | View protein in Pfam PF03165, MH1, 1 hit PF03166, MH2, 1 hit |
SMARTi | View protein in SMART SM00523, DWA, 1 hit SM00524, DWB, 1 hit |
SUPFAMi | SSF49879, SSF49879, 1 hit SSF56366, SSF56366, 1 hit |
PROSITEi | View protein in PROSITE PS51075, MH1, 1 hit PS51076, MH2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SMAD5_HUMAN | |
Accessioni | Q99717Primary (citable) accession number: Q99717 Secondary accession number(s): O14688, Q15798, Q9UQA1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 4, 2001 |
Last sequence update: | May 1, 1997 | |
Last modified: | December 2, 2020 | |
This is version 208 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families