SMAD5
Mothers against decapentaplegic homolog 5
Also known as: Dwfc, JV5-1, MADH5, SMAD5_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q99717
- Gene
- SMAD5
- Ensembl
- ENSG00000113658
- Chromosome
- 5
- Canonical length
- 465 aa
- Protein class
- Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
Canonical amino-acid sequenceUniProt
465 residues, UniProt reviewed canonical sequence.
>Q99717|SMAD5
1 MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG
61 QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE
121 VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP
181 NNTPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP
241 MDTSNNMIPQ IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT
301 DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC
361 NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW
421 GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SMAD5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 26 nTPM
Expression across tissuesHPA
Tissue
- skin: 26 nTPM
- ovary: 24 nTPM
- endometrium: 24 nTPM
- placenta: 23 nTPM
- tongue: 20 nTPM
- parathyroid gland: 20 nTPM
Single-cell type
- leydig cells: 121 nCPM
- medullary thymic epithelial cells: 115 nCPM
- podocytes: 115 nCPM
- hepatocytes: 108 nCPM
- pancreatic islet cells: 106 nCPM
- peritubular myoid cells: 106 nCPM
Immune cell
- basophil: 92 nTPM
- eosinophil: 29 nTPM
- NK-cell: 21 nTPM
- plasmacytoid DC: 16 nTPM
- naive B-cell: 15 nTPM
- gdT-cell: 14 nTPM
Brain region
- cerebellum: 96 nTPM
- white matter: 63 nTPM
- basal ganglia: 61 nTPM
- thalamus: 59 nTPM
- cerebral cortex: 58 nTPM
- hypothalamus: 57 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.16
- gnomAD pLI
- 1
- gnomAD missense Z
- 3
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- anatomical structure morphogenesis
- anti-Mullerian hormone receptor signaling pathway
- BMP signaling pathway
- bone development
- cardiac conduction system development
- cardiac muscle contraction
- cartilage development
- cell differentiation
- embryonic pattern specification
- erythrocyte differentiation
- germ cell development
- intracellular iron ion homeostasis
- Mullerian duct regression
- negative regulation of apoptotic process
- negative regulation of Fas signaling pathway
- negative regulation of gene expression
- osteoblast differentiation
- osteoblast fate commitment
- positive regulation of DNA-templated transcription
- positive regulation of osteoblast differentiation
- positive regulation of transcription by RNA polymerase II
- regulation of transcription by RNA polymerase II
- signal transduction
- SMAD protein signal transduction
- stem cell differentiation
- transforming growth factor beta receptor signaling pathway
- ureteric bud development
Molecular functions
- DEAD/H-box RNA helicase binding
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- I-SMAD binding
- metal ion binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
- ubiquitin protein ligase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SMAD5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads SMAD5 as an antibody target. Whether an autoantibody or antibody against SMAD5 could matter depends on whether native SMAD5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SMAD5 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label SMAD5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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