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Entry version 204 (11 Dec 2019)
Sequence version 3 (23 Jan 2002)
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Protein

Growth/differentiation factor 5

Gene

GDF5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (PubMed:24098149, PubMed:21976273, PubMed:15530414, PubMed:25092592). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (PubMed:21976273). Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (By similarity). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205).By similarity7 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionCytokine, Growth factor
Biological processChondrogenesis

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-2129379 Molecules associated with elastic fibres

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P43026

SIGNOR Signaling Network Open Resource

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SIGNORi
P43026

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Growth/differentiation factor 5
Short name:
GDF-5
Alternative name(s):
Bone morphogenetic protein 14
Short name:
BMP-14
Cartilage-derived morphogenetic protein 1
Short name:
CDMP-1
Lipopolysaccharide-associated protein 4
Short name:
LAP-4
Short name:
LPS-associated protein 4
Radotermin
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:GDF5
Synonyms:BMP14, CDMP1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 20

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000125965.8

Human Gene Nomenclature Database

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HGNCi
HGNC:4220 GDF5

Online Mendelian Inheritance in Man (OMIM)

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MIMi
601146 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P43026

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Acromesomelic chondrodysplasia, Grebe type (AMDG)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive acromesomelic chondrodysplasia. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDG is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_017407400C → Y in AMDG. 1 PublicationCorresponds to variant dbSNP:rs74315387EnsemblClinVar.1
Acromesomelic chondrodysplasia, Hunter-Thompson type (AMDH)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive form of dwarfism. Patients have limb abnormalities, with the middle and distal segments being most affected and the lower limbs more affected than the upper. AMDH is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.
Related information in OMIM
Brachydactyly C (BDC)4 Publications
The disease is caused by mutations affecting the gene represented in this entry. Some BDC patients with GDF5 mutations also manifest clinical features of ASPED angel-shaped phalango-epiphyseal dysplasia (ASPED), an autosomal dominant skeletal abnormality characterized by a typical angel-shaped phalanx, brachydactyly, specific radiological findings, abnormal dentition, hip dysplasia, and delayed bone age. This suggests that BDC and ASPED are part of the same clinical spectrum (PubMed:22828468).1 Publication
Disease descriptionA form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type C is characterized by deformity of the middle and proximal phalanges of the second and third fingers, sometimes with hypersegmentation of the proximal phalanx. The ring finger may be essentially normal and project beyond the others.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037978173M → V in BDC. 1 PublicationCorresponds to variant dbSNP:rs28936397EnsemblClinVar.1
Natural variantiVAR_073139201T → P in BDC; decrease of induction of SMAD protein signal transduction with either BMPR1A or BMPR1B; less induction of chondrgenesis; no phosphorylation of SMAD1-SMAD5-SMAD8 protein complex; reduction of protein level; abnormal proteolysis product. 1 Publication1
Natural variantiVAR_074161203T → N in BDC. 1 Publication1
Natural variantiVAR_073140263L → P in BDC; no induction of SMAD protein signal transduction via BMPR1A; less induction of chondrgenesis; no phosphorylation of SMAD1-SMAD5-SMAD8 protein complex; reduction of protein level; abnormal proteolysis product. 1 Publication1
Natural variantiVAR_074162486V → M in BDC. 1 Publication1
Du Pan syndrome (DPS)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare autosomal recessive condition characterized by absence of the fibulae and severe acromesomelic limb shortening with small, non-functional toes. Although milder, the phenotype resembles the autosomal recessive Hunter-Thompson and Grebe types of acromesomelic chondrodysplasia.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054910378R → Q in DPS. 1 PublicationCorresponds to variant dbSNP:rs121909350EnsemblClinVar.1
Natural variantiVAR_054911436P → T in DPS. 1 PublicationCorresponds to variant dbSNP:rs121909351EnsemblClinVar.1
Natural variantiVAR_037979437Missing in DPS; located on the same allele as T-439 and L-440. 1 Publication1
Natural variantiVAR_037980439S → T in DPS; located on the same allele as L-437 del and L-440. 1 Publication1
Natural variantiVAR_037981440H → L in DPS; located on the same allele as L-437 del and T-439. 1 Publication1
Natural variantiVAR_017408441L → P in DPS, SYNS2 and BDA2; the mutant is almost inactive; loss of binding to BMPR1A and BMPR1B ectodomains; no induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation; impairs nuclear translocation of phosphotylated SMAD1-SMAD5-SMAD8 protein complex; no ability to induce SMAD protein signal transduction; binds to NOG. 3 PublicationsCorresponds to variant dbSNP:rs28936683EnsemblClinVar.1
Symphalangism, proximal 1B (SYM1B)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by the hereditary absence of the proximal interphalangeal joints. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conductive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054909373L → R in SYM1B; the mature GDF5 protein is detected as the wild-type in the supernatant derived from the mutant transfected cells. 1 PublicationCorresponds to variant dbSNP:rs121909349EnsemblClinVar.1
Natural variantiVAR_026545438R → L in SYNS2 and SYM1B; increased biological activity when compared to wild-type; normal binding to BMPR1B ectodomain but increased binding to that of BMPR1A. 2 PublicationsCorresponds to variant dbSNP:rs74315388EnsemblClinVar.1
Natural variantiVAR_037983491E → K in SYM1B. 1 PublicationCorresponds to variant dbSNP:rs74315389EnsemblClinVar.1
Multiple synostoses syndrome 2 (SYNS2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073141414W → R in SYNS2 and BDA1C; reduced interaction with NOG; reduces affinity to BMPR1A; impairs BMP signaling through BMPR1A; impairs chondrogenesis. 1 Publication1
Natural variantiVAR_026545438R → L in SYNS2 and SYM1B; increased biological activity when compared to wild-type; normal binding to BMPR1B ectodomain but increased binding to that of BMPR1A. 2 PublicationsCorresponds to variant dbSNP:rs74315388EnsemblClinVar.1
Natural variantiVAR_073142445N → K in SYNS2. 1 Publication1
Natural variantiVAR_073143445N → T in SYNS2; resistant to NOG inhibition; no change in binding with MPR1A and BMPR1B; strong induction of chondrogenesis. 1 Publication1
Natural variantiVAR_037982475S → N in SYNS2; reduction in binding affinity with BMPR2; no change in binding affinity with BMPR1A; no change in binding affinity with BMPR1B; decreases induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation; delay of phosphotylated SMAD1-SMAD5-SMAD8 protein complex nuclear translocation; strong reduction of SMAD protein signal transduction; reduction of chondrocyte differentiation; strong improvement of chondrogenesis; decrease of NOG binding; resistant to NOG inhibition; no chondrogenesis inhibition. 2 PublicationsCorresponds to variant dbSNP:rs121909347EnsemblClinVar.1
Brachydactyly A2 (BDA2)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046743380R → Q in BDA2; reduces activity; impairs processing. 1 PublicationCorresponds to variant dbSNP:rs397514668EnsemblClinVar.1
Natural variantiVAR_017408441L → P in DPS, SYNS2 and BDA2; the mutant is almost inactive; loss of binding to BMPR1A and BMPR1B ectodomains; no induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation; impairs nuclear translocation of phosphotylated SMAD1-SMAD5-SMAD8 protein complex; no ability to induce SMAD protein signal transduction; binds to NOG. 3 PublicationsCorresponds to variant dbSNP:rs28936683EnsemblClinVar.1
Osteoarthritis 5 (OS5)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement.
Related information in OMIM
Brachydactyly A1, C (BDA1C)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of brachydactyly type A1. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1C inheritance can be autosomal dominant or autosomal recessive. Autosomal dominant BDA1C has a milder phenotype.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064416399R → C in BDA1C; less effective than wild-type in stimulating chondrogenesis; impairs BMP signaling through BMPR1A. 2 PublicationsCorresponds to variant dbSNP:rs397514519EnsemblClinVar.1
Natural variantiVAR_073141414W → R in SYNS2 and BDA1C; reduced interaction with NOG; reduces affinity to BMPR1A; impairs BMP signaling through BMPR1A; impairs chondrogenesis. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi490Y → N: Resitant to NOG inhibition. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNET

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DisGeNETi
8200

MalaCards human disease database

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MalaCardsi
GDF5
MIMi112600 phenotype
113100 phenotype
200700 phenotype
201250 phenotype
228900 phenotype
610017 phenotype
612400 phenotype
615072 phenotype
615298 phenotype

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
2098 Acromesomelic dysplasia, Grebe type
968 Acromesomelic dysplasia, Hunter-Thompson type
63442 Angel-shaped phalango-epiphyseal dysplasia
93388 Brachydactyly type A1
93396 Brachydactyly type A2
93384 Brachydactyly type C
2639 Fibular aplasia-complex brachydactyly syndrome
3237 Multiple synostoses syndrome
3250 Proximal symphalangism

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA28635

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
P43026 Tbio

Chemistry databases

Drug and drug target database

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DrugBanki
DB02325 Isopropyl alcohol

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
GDF5

Domain mapping of disease mutations (DMDM)

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DMDMi
20141384

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 27Sequence analysisAdd BLAST27
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_000003391228 – 381Sequence analysisAdd BLAST354
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000033913382 – 501Growth/differentiation factor 5Add BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi189N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi400 ↔ 4661 Publication
Disulfide bondi429 ↔ 4981 Publication
Disulfide bondi433 ↔ 5001 Publication
Disulfide bondi465InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P43026

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P43026

PeptideAtlas

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PeptideAtlasi
P43026

PRoteomics IDEntifications database

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PRIDEi
P43026

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
55574

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P43026

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P43026

SwissPalm database of S-palmitoylation events

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SwissPalmi
P43026

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Predominantly expressed in long bones during embryonic development. Expressed in monocytes (at protein level).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000125965 Expressed in 110 organ(s), highest expression level in saliva-secreting gland

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P43026 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P43026 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA015648

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; disulfide-linked (By similarity).

Interacts with serine proteases, HTRA1 and HTRA3 (By similarity). Following LPS binding, may form a complex with CXCR4, HSP90AA1 and HSPA8.

Interacts with high affinity with NOG; inhibits chondrogenesis.

Interacts with high affinity with BMPR1B and lower affinity with BMPR1A; positively regulates chondrocyte differentiation and induces SMAD dependent signaling.

Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631).

By similarity6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

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GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
113839, 30 interactors

Database of interacting proteins

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DIPi
DIP-5823N

Protein interaction database and analysis system

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IntActi
P43026, 26 interactors

Molecular INTeraction database

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MINTi
P43026

STRING: functional protein association networks

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STRINGi
9606.ENSP00000363492

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
P43026 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1501
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P43026

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P43026

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG3900 Eukaryota
ENOG410XT8Z LUCA

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000231514

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P43026

KEGG Orthology (KO)

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KOi
K04664

Database of Orthologous Groups

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OrthoDBi
798576at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P43026

TreeFam database of animal gene trees

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TreeFami
TF316134

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.10.90.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS

The PANTHER Classification System

More...
PANTHERi
PTHR11848 PTHR11848, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00204 TGFB, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF57501 SSF57501, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

P43026-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MRLPKLLTFL LWYLAWLDLE FICTVLGAPD LGQRPQGTRP GLAKAEAKER
60 70 80 90 100
PPLARNVFRP GGHSYGGGAT NANARAKGGT GQTGGLTQPK KDEPKKLPPR
110 120 130 140 150
PGGPEPKPGH PPQTRQATAR TVTPKGQLPG GKAPPKAGSV PSSFLLKKAR
160 170 180 190 200
EPGPPREPKE PFRPPPITPH EYMLSLYRTL SDADRKGGNS SVKLEAGLAN
210 220 230 240 250
TITSFIDKGQ DDRGPVVRKQ RYVFDISALE KDGLLGAELR ILRKKPSDTA
260 270 280 290 300
KPAAPGGGRA AQLKLSSCPS GRQPASLLDV RSVPGLDGSG WEVFDIWKLF
310 320 330 340 350
RNFKNSAQLC LELEAWERGR AVDLRGLGFD RAARQVHEKA LFLVFGRTKK
360 370 380 390 400
RDLFFNEIKA RSGQDDKTVY EYLFSQRRKR RAPLATRQGK RPSKNLKARC
410 420 430 440 450
SRKALHVNFK DMGWDDWIIA PLEYEAFHCE GLCEFPLRSH LEPTNHAVIQ
460 470 480 490 500
TLMNSMDPES TPPTCCVPTR LSPISILFID SANNVVYKQY EDMVVESCGC

R
Length:501
Mass (Da):55,411
Last modified:January 23, 2002 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i37985F2D15C4F5EF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti38T → S in AAA57007 (PubMed:7961761).Curated1
Sequence conflicti254 – 258APGGG → VPRSR in AAA57007 (PubMed:7961761).Curated5
Sequence conflicti321A → T in AAA57007 (PubMed:7961761).Curated1
Sequence conflicti384L → S in AAA57007 (PubMed:7961761).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037977163R → G. Corresponds to variant dbSNP:rs34534075Ensembl.1
Natural variantiVAR_037978173M → V in BDC. 1 PublicationCorresponds to variant dbSNP:rs28936397EnsemblClinVar.1
Natural variantiVAR_073139201T → P in BDC; decrease of induction of SMAD protein signal transduction with either BMPR1A or BMPR1B; less induction of chondrgenesis; no phosphorylation of SMAD1-SMAD5-SMAD8 protein complex; reduction of protein level; abnormal proteolysis product. 1 Publication1
Natural variantiVAR_074161203T → N in BDC. 1 Publication1
Natural variantiVAR_073140263L → P in BDC; no induction of SMAD protein signal transduction via BMPR1A; less induction of chondrgenesis; no phosphorylation of SMAD1-SMAD5-SMAD8 protein complex; reduction of protein level; abnormal proteolysis product. 1 Publication1
Natural variantiVAR_026120276S → A2 PublicationsCorresponds to variant dbSNP:rs224331Ensembl.1
Natural variantiVAR_054909373L → R in SYM1B; the mature GDF5 protein is detected as the wild-type in the supernatant derived from the mutant transfected cells. 1 PublicationCorresponds to variant dbSNP:rs121909349EnsemblClinVar.1
Natural variantiVAR_054910378R → Q in DPS. 1 PublicationCorresponds to variant dbSNP:rs121909350EnsemblClinVar.1
Natural variantiVAR_046743380R → Q in BDA2; reduces activity; impairs processing. 1 PublicationCorresponds to variant dbSNP:rs397514668EnsemblClinVar.1
Natural variantiVAR_064416399R → C in BDA1C; less effective than wild-type in stimulating chondrogenesis; impairs BMP signaling through BMPR1A. 2 PublicationsCorresponds to variant dbSNP:rs397514519EnsemblClinVar.1
Natural variantiVAR_017407400C → Y in AMDG. 1 PublicationCorresponds to variant dbSNP:rs74315387EnsemblClinVar.1
Natural variantiVAR_073141414W → R in SYNS2 and BDA1C; reduced interaction with NOG; reduces affinity to BMPR1A; impairs BMP signaling through BMPR1A; impairs chondrogenesis. 1 Publication1
Natural variantiVAR_054911436P → T in DPS. 1 PublicationCorresponds to variant dbSNP:rs121909351EnsemblClinVar.1
Natural variantiVAR_037979437Missing in DPS; located on the same allele as T-439 and L-440. 1 Publication1
Natural variantiVAR_026545438R → L in SYNS2 and SYM1B; increased biological activity when compared to wild-type; normal binding to BMPR1B ectodomain but increased binding to that of BMPR1A. 2 PublicationsCorresponds to variant dbSNP:rs74315388EnsemblClinVar.1
Natural variantiVAR_037980439S → T in DPS; located on the same allele as L-437 del and L-440. 1 Publication1
Natural variantiVAR_037981440H → L in DPS; located on the same allele as L-437 del and T-439. 1 Publication1
Natural variantiVAR_017408441L → P in DPS, SYNS2 and BDA2; the mutant is almost inactive; loss of binding to BMPR1A and BMPR1B ectodomains; no induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation; impairs nuclear translocation of phosphotylated SMAD1-SMAD5-SMAD8 protein complex; no ability to induce SMAD protein signal transduction; binds to NOG. 3 PublicationsCorresponds to variant dbSNP:rs28936683EnsemblClinVar.1
Natural variantiVAR_073142445N → K in SYNS2. 1 Publication1
Natural variantiVAR_073143445N → T in SYNS2; resistant to NOG inhibition; no change in binding with MPR1A and BMPR1B; strong induction of chondrogenesis. 1 Publication1
Natural variantiVAR_037982475S → N in SYNS2; reduction in binding affinity with BMPR2; no change in binding affinity with BMPR1A; no change in binding affinity with BMPR1B; decreases induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation; delay of phosphotylated SMAD1-SMAD5-SMAD8 protein complex nuclear translocation; strong reduction of SMAD protein signal transduction; reduction of chondrocyte differentiation; strong improvement of chondrogenesis; decrease of NOG binding; resistant to NOG inhibition; no chondrogenesis inhibition. 2 PublicationsCorresponds to variant dbSNP:rs121909347EnsemblClinVar.1
Natural variantiVAR_074162486V → M in BDC. 1 Publication1
Natural variantiVAR_037983491E → K in SYM1B. 1 PublicationCorresponds to variant dbSNP:rs74315389EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
X80915 Genomic DNA Translation: CAA56874.1
U13660 mRNA Translation: AAA57007.1
AL121586 Genomic DNA Translation: CAB89416.1
CH471077 Genomic DNA Translation: EAW76208.1
CH471077 Genomic DNA Translation: EAW76209.1
BC032495 mRNA Translation: AAH32495.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS13254.1

Protein sequence database of the Protein Information Resource

More...
PIRi
A55452
JC2347

NCBI Reference Sequences

More...
RefSeqi
NP_000548.2, NM_000557.4
NP_001306067.1, NM_001319138.1
XP_011527377.1, XM_011529075.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000374369; ENSP00000363489; ENSG00000125965
ENST00000374372; ENSP00000363492; ENSG00000125965

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
8200

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:8200

UCSC genome browser

More...
UCSCi
uc002xck.2 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

GDF5 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80915 Genomic DNA Translation: CAA56874.1
U13660 mRNA Translation: AAA57007.1
AL121586 Genomic DNA Translation: CAB89416.1
CH471077 Genomic DNA Translation: EAW76208.1
CH471077 Genomic DNA Translation: EAW76209.1
BC032495 mRNA Translation: AAH32495.1
CCDSiCCDS13254.1
PIRiA55452
JC2347
RefSeqiNP_000548.2, NM_000557.4
NP_001306067.1, NM_001319138.1
XP_011527377.1, XM_011529075.2

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WAQX-ray2.28A387-501[»]
2BHKX-ray2.40A382-501[»]
3EVSX-ray2.10B387-501[»]
3QB4X-ray2.28A/C387-501[»]
5HK5X-ray2.90A/B/C/D382-501[»]
SMRiP43026
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi113839, 30 interactors
DIPiDIP-5823N
IntActiP43026, 26 interactors
MINTiP43026
STRINGi9606.ENSP00000363492

Chemistry databases

DrugBankiDB02325 Isopropyl alcohol

PTM databases

iPTMnetiP43026
PhosphoSitePlusiP43026
SwissPalmiP43026

Polymorphism and mutation databases

BioMutaiGDF5
DMDMi20141384

Proteomic databases

EPDiP43026
PaxDbiP43026
PeptideAtlasiP43026
PRIDEiP43026
ProteomicsDBi55574

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
8200

Genome annotation databases

EnsembliENST00000374369; ENSP00000363489; ENSG00000125965
ENST00000374372; ENSP00000363492; ENSG00000125965
GeneIDi8200
KEGGihsa:8200
UCSCiuc002xck.2 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
8200
DisGeNETi8200
EuPathDBiHostDB:ENSG00000125965.8

GeneCards: human genes, protein and diseases

More...
GeneCardsi
GDF5
HGNCiHGNC:4220 GDF5
HPAiHPA015648
MalaCardsiGDF5
MIMi112600 phenotype
113100 phenotype
200700 phenotype
201250 phenotype
228900 phenotype
601146 gene
610017 phenotype
612400 phenotype
615072 phenotype
615298 phenotype
neXtProtiNX_P43026
Orphaneti2098 Acromesomelic dysplasia, Grebe type
968 Acromesomelic dysplasia, Hunter-Thompson type
63442 Angel-shaped phalango-epiphyseal dysplasia
93388 Brachydactyly type A1
93396 Brachydactyly type A2
93384 Brachydactyly type C
2639 Fibular aplasia-complex brachydactyly syndrome
3237 Multiple synostoses syndrome
3250 Proximal symphalangism
PharmGKBiPA28635

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
HOGENOMiHOG000231514
InParanoidiP43026
KOiK04664
OrthoDBi798576at2759
PhylomeDBiP43026
TreeFamiTF316134

Enzyme and pathway databases

ReactomeiR-HSA-2129379 Molecules associated with elastic fibres
SignaLinkiP43026
SIGNORiP43026

Miscellaneous databases

EvolutionaryTraceiP43026

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
GDF5

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
8200
PharosiP43026 Tbio

Protein Ontology

More...
PROi
PR:P43026
RNActiP43026 protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000125965 Expressed in 110 organ(s), highest expression level in saliva-secreting gland
ExpressionAtlasiP43026 baseline and differential
GenevisibleiP43026 HS

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiGDF5_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P43026
Secondary accession number(s): E1P5Q2, Q96SB1
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2002
Last modified: December 11, 2019
This is version 204 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
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