InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GDF5

Summary

InnateDB Protein

IDBP-70040.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

GDF5

Protein Name

growth differentiation factor 5

Synonyms

BDA1C; BMP-14; BMP14; CDMP1; LAP-4; LAP4; OS5; SYM1B; SYNS2;

Species

Homo sapiens

Ensembl Protein

ENSP00000363492

InnateDB Gene

IDBG-70038 (GDF5)

Protein Structure

UniProt Annotation

Function

Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (By similarity). Could be involved in bone and cartilage formation. Chondrogenic signaling is mediated by the high-affinity receptor BMPR1B. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes. {ECO:0000250, ECO:0000269PubMed:11276205, ECO:0000269PubMed:15530414, ECO:0000269PubMed:19229295}.

Subcellular Localization

Secreted {ECO:0000269PubMed:11276205}. Cell membrane {ECO:0000269PubMed:11276205}.

Disease Associations

Acromesomelic chondrodysplasia, Grebe type (AMDG) [MIM:200700]: An 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. {ECO:0000269PubMed:9288098}. Note=The disease is caused by mutations affecting the gene represented in this entry.Acromesomelic chondrodysplasia, Hunter-Thompson type (AMDH) [MIM:201250]: An 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. Note=The disease is caused by mutations affecting the gene represented in this entry.Brachydactyly C (BDC) [MIM:113100]: A 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. {ECO:0000269PubMed:14735582, ECO:0000269PubMed:22828468}. Note=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). {ECO:0000269PubMed:22828468}.Du Pan syndrome (DPS) [MIM:228900]: Rare 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. {ECO:0000269PubMed:12121354, ECO:0000269PubMed:16222676, ECO:0000269PubMed:18629880}. Note=The disease is caused by mutations affecting the gene represented in this entry.Symphalangism, proximal 1B (SYM1B) [MIM:615298]: A 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. {ECO:0000269PubMed:16127465, ECO:0000269PubMed:16892395, ECO:0000269PubMed:18283415}. Note=The disease is caused by mutations affecting the gene represented in this entry.Multiple synostoses syndrome 2 (SYNS2) [MIM:610017]: A 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. {ECO:0000269PubMed:16532400, ECO:0000269Ref.11}. Note=The disease is caused by mutations affecting the gene represented in this entry.Brachydactyly A2 (BDA2) [MIM:112600]: A 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. {ECO:0000269PubMed:16127465, ECO:0000269PubMed:18203755}. Note=The disease is caused by mutations affecting the gene represented in this entry.Osteoarthritis 5 (OS5) [MIM:612400]: A 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Brachydactyly A1, C (BDA1C) [MIM:615072]: A 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. {ECO:0000269PubMed:20683927}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Predominantly expressed in long bones during embryonic development. Expressed in monocytes (at protein level). {ECO:0000269PubMed:11276205}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 10 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	10 [view]
Protein-Protein	9 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005102	receptor binding
GO:0005125	cytokine activity
GO:0005515	protein binding
GO:0008083	growth factor activity

Biological Process

GO:0002062	chondrocyte differentiation
GO:0007178	transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007267	cell-cell signaling
GO:0030198	extracellular matrix organization
GO:0030326	embryonic limb morphogenesis
GO:0032332	positive regulation of chondrocyte differentiation
GO:0035136	forelimb morphogenesis
GO:0035137	hindlimb morphogenesis
GO:0040007	growth
GO:0040014	regulation of multicellular organism growth
GO:0043524	negative regulation of neuron apoptotic process
GO:0045666	positive regulation of neuron differentiation
GO:0050680	negative regulation of epithelial cell proliferation
GO:2001054	negative regulation of mesenchymal cell apoptotic process