Gdf5

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 (By similarity). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (By similarity). Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (PubMed:24076600). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (By similarity).By similarity1 Publication

GO - Molecular functionⁱ

BMP binding Source: MGI
cytokine activity Source: GO_Central
growth factor activity Source: UniProtKB-KW
identical protein binding Source: MGI
signaling receptor binding Source: MGI
transforming growth factor beta receptor binding Source: GO_Central

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cell development Source: GO_Central
chondroblast differentiation Source: MGI
chondrocyte differentiation
Source: MGI
Inferred from genetic interactionⁱ
- 18363966
embryonic limb morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 15542031
forelimb morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 8145850
hindlimb morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 17085896
- 8145850
negative regulation of chondrocyte differentiation Source: MGI
negative regulation of epithelial cell proliferation Source: MGI
negative regulation of mesenchymal cell apoptotic process
Source: MGI
Inferred from mutant phenotypeⁱ
- 15542031
negative regulation of neuron apoptotic process Source: MGI
ossification involved in bone remodeling Source: Ensembl
positive regulation of BMP signaling pathway Source: MGI
positive regulation of chondrocyte differentiation
Source: MGI
Inferred from direct assayⁱ
- 9885252
positive regulation of neuron differentiation Source: MGI
positive regulation of pathway-restricted SMAD protein phosphorylation Source: GO_Central
regulation of MAPK cascade Source: GO_Central
regulation of multicellular organism growth
Source: MGI
Inferred from mutant phenotypeⁱ
- 17085896
regulation of SMAD protein signal transduction Source: MGI
response to mechanical stimulus Source: Ensembl
SMAD protein signal transduction Source: MGI
transmembrane receptor protein serine/threonine kinase signaling pathway
Source: MGI
Inferred from genetic interactionⁱ
- 18363966

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Cytokine, Growth factor
Biological process	Chondrogenesis

Enzyme and pathway databases

Reactomeⁱ	R-MMU-2129379 Molecules associated with elastic fibres

Reactomeⁱ

R-MMU-2129379 Molecules associated with elastic fibres

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Growth/differentiation factor 5 Short name: GDF-5 Alternative name(s): Bone morphogenetic protein 14 Short name: BMP-14
Gene namesⁱ	Name:Gdf5 Synonyms:Bmp14, Bp, Gdf-5
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 2

Organism-specific databases

MGIⁱ	MGI:95688 Gdf5

Keywords - Cellular componentⁱ

Cell membrane, Membrane, Secreted

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Defects in Gdf5 are the cause of brachypodism (bp) which alters the length and numbers of bones in the limbs but spares the axial skeleton.1 Publication

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
Signal peptideⁱ	1 – 27	Sequence analysisAdd BLAST	27
PropeptideⁱPRO_0000033914	28 – 375	Sequence analysisAdd BLAST	348
ChainⁱPRO_0000033915	376 – 495	Growth/differentiation factor 5Add BLAST	120

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Glycosylationⁱ	183	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	394 ↔ 460	By similarity
Disulfide bondⁱ	423 ↔ 492	By similarity
Disulfide bondⁱ	427 ↔ 494	By similarity
Disulfide bondⁱ	459	InterchainBy similarity

Keywords - PTMⁱ

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbⁱ	P43027
PRIDEⁱ	P43027

PTM databases

iPTMnetⁱ	P43027
PhosphoSitePlusⁱ	P43027

Expressionⁱ

Inductionⁱ

Gene expression databases

Bgeeⁱ	ENSMUSG00000038259 Expressed in 121 organ(s), highest expression level in limb bud
CleanExⁱ	MM_GDF5
Genevisibleⁱ	P43027 MM

Interactionⁱ

Subunit structureⁱ

Homodimer; disulfide-linked (By similarity). Interacts with serine proteases, HTRA1 and HTRA3 (PubMed:15206957, PubMed:14973287). Following LPS binding, may form a complex with CXCR4, HSP90AA1 and HSPA8 (By similarity). Interacts with high affinity with NOG; inhibits chondrogenesis (By similarity). 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 (By similarity).By similarity2 Publications

GO - Molecular functionⁱ

BMP binding Source: MGI
cytokine activity Source: GO_Central
growth factor activity Source: UniProtKB-KW
identical protein binding Source: MGI
signaling receptor binding Source: MGI
transforming growth factor beta receptor binding Source: GO_Central

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	199888, 2 interactors
STRINGⁱ	10090.ENSMUSP00000048079

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	P43027
SMRⁱ	P43027
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the TGF-beta family.Curated

Keywords - Domainⁱ

Signal

Phylogenomic databases

eggNOGⁱ	KOG3900 Eukaryota ENOG410XT8Z LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000118883
HOGENOMⁱ	HOG000231514
HOVERGENⁱ	HBG107938
InParanoidⁱ	P43027
KEGG Orthology (KO) More...KOⁱ	K04664
OMAⁱ	LCEFPLR
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G09KP
TreeFamⁱ	TF316134

Family and domain databases

Gene3Dⁱ	2.10.90.10, 1 hit
InterProⁱ	View protein in InterPro IPR029034 Cystine-knot_cytokine IPR001839 TGF-b_C IPR001111 TGF-b_propeptide IPR015615 TGF-beta-rel IPR017948 TGFb_CS
PANTHERⁱ	PTHR11848 PTHR11848, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00019 TGF_beta, 1 hit PF00688 TGFb_propeptide, 1 hit
SMARTⁱ	View protein in SMART SM00204 TGFB, 1 hit
SUPFAMⁱ	SSF57501 SSF57501, 1 hit
PROSITEⁱ	View protein in PROSITE PS00250 TGF_BETA_1, 1 hit PS51362 TGF_BETA_2, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

P43027-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MRLPKLLTLL LWHLAWLDLE LICTVLGAPD LGQRTPGAKP GLTKAEAKER 
        60         70         80         90        100
PPLARNVFRP GGHIYGVGAT NARAKGSSGQ TQAKKDEPRK MPPRSGGPET 
       110        120        130        140        150
KPGPSSQTRQ AAARTVTPKG QLPGGKASSK AGSAPSSFLL KKTREPGTPR 
       160        170        180        190        200
EPKEPFRPPP ITPHEYMLSL YRTLSDADRK GGNSSVKLEA GLANTITSFI 
       210        220        230        240        250
DKGQDDRGPA VRKQRYVFDI SALEKDGLLG AELRILRKKP LDVAKPAVPS 
       260        270        280        290        300
SGRVAQLKLS SCPSGRQPAA LLDVRSVPGL DGSGWEVFDI WKLFRNFKNS 
       310        320        330        340        350
AQLCLELEAW ERGRAVDLRG LGFERTARQV HEKALFLVFG RTKKRDLFFN 
       360        370        380        390        400
EIKARSGQDD KTVYEYLFSQ RRKRRAPLAN RQGKRPSKNL KARCSRKALH 
       410        420        430        440        450
VNFKDMGWDD WIIAPLEYEA FHCEGLCEFP LRSHLEPTNH AVIQTLMNSM 
       460        470        480        490 
DPESTPPTCC VPTRLSPISI LFIDSANNVV YKQYEDMVVE SCGCR

Length:495

Mass (Da):54,895

Last modified:July 27, 2011 - v2

Checksum:ⁱ8FAECD5A9C996D6E

GO

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱ	98	P → S2 Publications		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U08337 mRNA Translation: AAA18778.1 AL845445 Genomic DNA Translation: CAM22612.1 CH466551 Genomic DNA Translation: EDL06156.1 BC034546 mRNA Translation: AAH34546.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS16958.1
PIRⁱ	S43294
NCBI Reference Sequences More...RefSeqⁱ	NP_032135.2, NM_008109.3
UniGeneⁱ	Mm.4744

Genome annotation databases

Ensemblⁱ	ENSMUST00000040162; ENSMUSP00000048079; ENSMUSG00000038259
GeneIDⁱ	14563
KEGGⁱ	mmu:14563
UCSC genome browser More...UCSCⁱ	uc012chg.1 mouse

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P43027	Uncharacterized protein (Fragment)		MOUSE		249	UniRef100_P43027

Protein	Similar proteins		Species	Score	Length	Source
P43027	Growth/differentiation factor 5	)	HUMAN		501	UniRef90_P43026
Growth/differentiation factor 5 (Fragment)		ESCRO		508
GDF5 isoform 1		PANTR		501
GDF5 isoform 1		PONAB		501
Uncharacterized protein		CALJA		501
+123

Protein	Similar proteins		Species	Score	Length	Source
P43027	Growth/differentiation factor 5	)	HUMAN		501	UniRef50_P43026
Growth/differentiation factor 5 (Fragment)		ESCRO		508
Uncharacterized protein		AOTNA		501
Uncharacterized protein		Cebus capucinus imitator		501
Uncharacterized protein		PANPA		501
+260

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U08337 mRNA Translation: AAA18778.1 AL845445 Genomic DNA Translation: CAM22612.1 CH466551 Genomic DNA Translation: EDL06156.1 BC034546 mRNA Translation: AAH34546.1
CCDSⁱ	CCDS16958.1
PIRⁱ	S43294
RefSeqⁱ	NP_032135.2, NM_008109.3
UniGeneⁱ	Mm.4744

3D structure databases

ProteinModelPortalⁱ	P43027
SMRⁱ	P43027
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	199888, 2 interactors
STRINGⁱ	10090.ENSMUSP00000048079

PTM databases

iPTMnetⁱ	P43027
PhosphoSitePlusⁱ	P43027

Proteomic databases

PaxDbⁱ	P43027
PRIDEⁱ	P43027

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000040162; ENSMUSP00000048079; ENSMUSG00000038259
GeneIDⁱ	14563
KEGGⁱ	mmu:14563
UCSCⁱ	uc012chg.1 mouse

Organism-specific databases

CTDⁱ	8200
MGIⁱ	MGI:95688 Gdf5

Phylogenomic databases

eggNOGⁱ	KOG3900 Eukaryota ENOG410XT8Z LUCA
GeneTreeⁱ	ENSGT00760000118883
HOGENOMⁱ	HOG000231514
HOVERGENⁱ	HBG107938
InParanoidⁱ	P43027
KOⁱ	K04664
OMAⁱ	LCEFPLR
OrthoDBⁱ	EOG091G09KP
TreeFamⁱ	TF316134

Enzyme and pathway databases

Reactomeⁱ	R-MMU-2129379 Molecules associated with elastic fibres

Reactomeⁱ

R-MMU-2129379 Molecules associated with elastic fibres

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:P43027
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000038259 Expressed in 121 organ(s), highest expression level in limb bud
CleanExⁱ	MM_GDF5
Genevisibleⁱ	P43027 MM

Family and domain databases

Gene3Dⁱ	2.10.90.10, 1 hit
InterProⁱ	View protein in InterPro IPR029034 Cystine-knot_cytokine IPR001839 TGF-b_C IPR001111 TGF-b_propeptide IPR015615 TGF-beta-rel IPR017948 TGFb_CS
PANTHERⁱ	PTHR11848 PTHR11848, 1 hit
Pfamⁱ	View protein in Pfam PF00019 TGF_beta, 1 hit PF00688 TGFb_propeptide, 1 hit
SMARTⁱ	View protein in SMART SM00204 TGFB, 1 hit
SUPFAMⁱ	SSF57501 SSF57501, 1 hit
PROSITEⁱ	View protein in PROSITE PS00250 TGF_BETA_1, 1 hit PS51362 TGF_BETA_2, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	GDF5_MOUSE
Accessionⁱ	P43027Primary (citable) accession number: P43027 Secondary accession number(s): A2ARK2
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
	Last sequence update:	July 27, 2011
	Last modified:	September 12, 2018
	This is version 159 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P43027 (GDF5_MOUSE)

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Growth/differentiation factor 5

Select a section on the left to see content.

<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

<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

Enzyme and pathway databases

<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

Organism-specific databases

<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

Plasma membrane

Extracellular region or secreted

Plasma Membrane

Keywords - Cellular componenti

<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 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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

<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

GO - Molecular functioni

Protein-protein interaction databases

<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

3D structure databases

<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

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<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 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

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ