Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Growth/differentiation factor 5

Gene

GDF5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Molecular functioni

  • BMP binding Source: UniProtKB
  • cytokine activity Source: GO_Central
  • growth factor activity Source: ProtInc
  • identical protein binding Source: IntAct
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Chondrogenesis

Enzyme and pathway databases

ReactomeiREACT_150331. Molecules associated with elastic fibres.
SignaLinkiP43026.

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
Cartilage-derived morphogenetic protein 1
Short name:
CDMP-1
Lipopolysaccharide-associated protein 4
Short name:
LAP-4
Short name:
LPS-associated protein 4
Radotermin
Gene namesi
Name:GDF5
Synonyms:BMP14, CDMP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:4220. GDF5.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

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.

See also OMIM:200700
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti400 – 4001C → Y in AMDG. 1 Publication
VAR_017407
Acromesomelic chondrodysplasia, Hunter-Thompson type (AMDH)

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.

See also OMIM:201250
Brachydactyly C (BDC)3 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).

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.

See also OMIM:113100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti173 – 1731M → V in BDC. 1 Publication
Corresponds to variant rs28936397 [ dbSNP | Ensembl ].
VAR_037978
Natural varianti201 – 2011T → 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 Publication
VAR_073139
Natural varianti263 – 2631L → 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 Publication
VAR_073140
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.

See also OMIM:228900
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti378 – 3781R → Q in DPS. 1 Publication
VAR_054910
Natural varianti436 – 4361P → T in DPS. 1 Publication
VAR_054911
Natural varianti437 – 4371Missing in DPS; located on the same allele as T-439 and L-440. 1 Publication
VAR_037979
Natural varianti439 – 4391S → T in DPS; located on the same allele as L-437 del and L-440. 1 Publication
VAR_037980
Natural varianti440 – 4401H → L in DPS; located on the same allele as L-437 del and T-439. 1 Publication
VAR_037981
Natural varianti441 – 4411L → 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 Publications
Corresponds to variant rs28936683 [ dbSNP | Ensembl ].
VAR_017408
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.

See also OMIM:615298
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti373 – 3731L → R in SYM1B; the mature GDF5 protein is detected as the wild-type in the supernatant derived from the mutant transfected cells. 1 Publication
VAR_054909
Natural varianti438 – 4381R → 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 Publications
VAR_026545
Natural varianti491 – 4911E → K in SYM1B. 1 Publication
VAR_037983
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.

See also OMIM:610017
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti414 – 4141W → R in SYNS2 and BDA1C; reduced interaction with NOG; reduces affinity to BMPR1A; impairs BMP signaling through BMPR1A; impairs chondrogenesis. 1 Publication
VAR_073141
Natural varianti438 – 4381R → 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 Publications
VAR_026545
Natural varianti441 – 4411L → 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 Publications
Corresponds to variant rs28936683 [ dbSNP | Ensembl ].
VAR_017408
Natural varianti445 – 4451N → K in SYNS2. 1 Publication
VAR_073142
Natural varianti445 – 4451N → T in SYNS2; resistant to NOG inhibition; no change in binding with MPR1A and BMPR1B; strong induction of chondrogenesis. 1 Publication
VAR_073143
Natural varianti475 – 4751S → 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 Publications
VAR_037982
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.

See also OMIM:112600
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti380 – 3801R → Q in BDA2; reduces activity; impairs processing. 1 Publication
VAR_046743
Natural varianti441 – 4411L → 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 Publications
Corresponds to variant rs28936683 [ dbSNP | Ensembl ].
VAR_017408
Osteoarthritis 5 (OS5)

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.

See also OMIM:612400
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.

See also OMIM:615072
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti399 – 3991R → C in BDA1C; less effective than wild-type in stimulating chondrogenesis; impairs BMP signaling through BMPR1A. 2 Publications
VAR_064416
Natural varianti414 – 4141W → R in SYNS2 and BDA1C; reduced interaction with NOG; reduces affinity to BMPR1A; impairs BMP signaling through BMPR1A; impairs chondrogenesis. 1 Publication
VAR_073141

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

MIMi112600. phenotype.
113100. phenotype.
200700. phenotype.
201250. phenotype.
228900. phenotype.
610017. phenotype.
612400. phenotype.
615072. phenotype.
615298. phenotype.
Orphaneti2098. Acromesomelic dysplasia, Grebe type.
968. Acromesomelic dysplasia, Hunter-Thomson type.
63442. Angel-shaped phalango-epiphyseal dysplasia.
93388. Brachydactyly type A1.
93396. Brachydactyly type A2.
93384. Brachydactyly type C.
2639. Fibular aplasia - complex brachydactyly.
3237. Multiple synostoses syndrome.
3250. Proximal symphalangism.
PharmGKBiPA28635.

Polymorphism and mutation databases

BioMutaiGDF5.
DMDMi20141384.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Propeptidei28 – 381354Sequence AnalysisPRO_0000033912Add
BLAST
Chaini382 – 501120Growth/differentiation factor 5PRO_0000033913Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi189 – 1891N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi400 ↔ 4661 Publication
Disulfide bondi429 ↔ 4981 Publication
Disulfide bondi433 ↔ 5001 Publication
Disulfide bondi465 – 465InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP43026.
PRIDEiP43026.

PTM databases

PhosphoSiteiP43026.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP43026.
CleanExiHS_GDF5.
ExpressionAtlasiP43026. baseline and differential.
GenevestigatoriP43026.

Organism-specific databases

HPAiHPA015648.

Interactioni

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.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-8571476,EBI-8571476
BMPR1AP368943EBI-8571476,EBI-1029237
BMPR1BO002387EBI-8571476,EBI-7527193
BMPR2Q138734EBI-8571476,EBI-527196

Protein-protein interaction databases

BioGridi113839. 28 interactions.
DIPiDIP-5823N.
IntActiP43026. 4 interactions.
MINTiMINT-7264433.
STRINGi9606.ENSP00000363489.

Structurei

Secondary structure

1
501
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi399 – 4035Combined sources
Beta strandi406 – 4083Combined sources
Helixi410 – 4123Combined sources
Helixi414 – 4163Combined sources
Beta strandi418 – 4203Combined sources
Beta strandi422 – 4254Combined sources
Beta strandi428 – 4325Combined sources
Helixi439 – 4413Combined sources
Helixi445 – 45612Combined sources
Turni458 – 4603Combined sources
Beta strandi466 – 47914Combined sources
Beta strandi481 – 4833Combined sources
Beta strandi485 – 50016Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WAQX-ray2.28A387-501[»]
2BHKX-ray2.40A382-501[»]
3EVSX-ray2.10B387-501[»]
3QB4X-ray2.28A/C387-501[»]
ProteinModelPortaliP43026.
SMRiP43026. Positions 398-501.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43026.

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG317866.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43026.
KOiK04664.
OMAiPITPHEY.
OrthoDBiEOG7WMCK0.
PhylomeDBiP43026.
TreeFamiTF316134.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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
Checksum:i37985F2D15C4F5EF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti38 – 381T → S in AAA57007 (PubMed:7961761).Curated
Sequence conflicti254 – 2585APGGG → VPRSR in AAA57007 (PubMed:7961761).Curated
Sequence conflicti321 – 3211A → T in AAA57007 (PubMed:7961761).Curated
Sequence conflicti384 – 3841L → S in AAA57007 (PubMed:7961761).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti163 – 1631R → G.
Corresponds to variant rs34534075 [ dbSNP | Ensembl ].
VAR_037977
Natural varianti173 – 1731M → V in BDC. 1 Publication
Corresponds to variant rs28936397 [ dbSNP | Ensembl ].
VAR_037978
Natural varianti201 – 2011T → 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 Publication
VAR_073139
Natural varianti263 – 2631L → 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 Publication
VAR_073140
Natural varianti276 – 2761S → A.2 Publications
Corresponds to variant rs224331 [ dbSNP | Ensembl ].
VAR_026120
Natural varianti373 – 3731L → R in SYM1B; the mature GDF5 protein is detected as the wild-type in the supernatant derived from the mutant transfected cells. 1 Publication
VAR_054909
Natural varianti378 – 3781R → Q in DPS. 1 Publication
VAR_054910
Natural varianti380 – 3801R → Q in BDA2; reduces activity; impairs processing. 1 Publication
VAR_046743
Natural varianti399 – 3991R → C in BDA1C; less effective than wild-type in stimulating chondrogenesis; impairs BMP signaling through BMPR1A. 2 Publications
VAR_064416
Natural varianti400 – 4001C → Y in AMDG. 1 Publication
VAR_017407
Natural varianti414 – 4141W → R in SYNS2 and BDA1C; reduced interaction with NOG; reduces affinity to BMPR1A; impairs BMP signaling through BMPR1A; impairs chondrogenesis. 1 Publication
VAR_073141
Natural varianti436 – 4361P → T in DPS. 1 Publication
VAR_054911
Natural varianti437 – 4371Missing in DPS; located on the same allele as T-439 and L-440. 1 Publication
VAR_037979
Natural varianti438 – 4381R → 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 Publications
VAR_026545
Natural varianti439 – 4391S → T in DPS; located on the same allele as L-437 del and L-440. 1 Publication
VAR_037980
Natural varianti440 – 4401H → L in DPS; located on the same allele as L-437 del and T-439. 1 Publication
VAR_037981
Natural varianti441 – 4411L → 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 Publications
Corresponds to variant rs28936683 [ dbSNP | Ensembl ].
VAR_017408
Natural varianti445 – 4451N → K in SYNS2. 1 Publication
VAR_073142
Natural varianti445 – 4451N → T in SYNS2; resistant to NOG inhibition; no change in binding with MPR1A and BMPR1B; strong induction of chondrogenesis. 1 Publication
VAR_073143
Natural varianti475 – 4751S → 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 Publications
VAR_037982
Natural varianti491 – 4911E → K in SYM1B. 1 Publication
VAR_037983

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.
UniGeneiHs.1573.

Genome annotation databases

EnsembliENST00000374369; ENSP00000363489; ENSG00000125965.
ENST00000374372; ENSP00000363492; ENSG00000125965.
GeneIDi8200.
KEGGihsa:8200.
UCSCiuc002xck.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

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.
UniGeneiHs.1573.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WAQX-ray2.28A387-501[»]
2BHKX-ray2.40A382-501[»]
3EVSX-ray2.10B387-501[»]
3QB4X-ray2.28A/C387-501[»]
ProteinModelPortaliP43026.
SMRiP43026. Positions 398-501.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113839. 28 interactions.
DIPiDIP-5823N.
IntActiP43026. 4 interactions.
MINTiMINT-7264433.
STRINGi9606.ENSP00000363489.

PTM databases

PhosphoSiteiP43026.

Polymorphism and mutation databases

BioMutaiGDF5.
DMDMi20141384.

Proteomic databases

PaxDbiP43026.
PRIDEiP43026.

Protocols and materials databases

DNASUi8200.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374369; ENSP00000363489; ENSG00000125965.
ENST00000374372; ENSP00000363492; ENSG00000125965.
GeneIDi8200.
KEGGihsa:8200.
UCSCiuc002xck.1. human.

Organism-specific databases

CTDi8200.
GeneCardsiGC20M034021.
HGNCiHGNC:4220. GDF5.
HPAiHPA015648.
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-Thomson type.
63442. Angel-shaped phalango-epiphyseal dysplasia.
93388. Brachydactyly type A1.
93396. Brachydactyly type A2.
93384. Brachydactyly type C.
2639. Fibular aplasia - complex brachydactyly.
3237. Multiple synostoses syndrome.
3250. Proximal symphalangism.
PharmGKBiPA28635.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG317866.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43026.
KOiK04664.
OMAiPITPHEY.
OrthoDBiEOG7WMCK0.
PhylomeDBiP43026.
TreeFamiTF316134.

Enzyme and pathway databases

ReactomeiREACT_150331. Molecules associated with elastic fibres.
SignaLinkiP43026.

Miscellaneous databases

EvolutionaryTraceiP43026.
GeneWikiiGDF5.
GenomeRNAii8200.
NextBioi30902.
PROiP43026.
SOURCEiSearch...

Gene expression databases

BgeeiP43026.
CleanExiHS_GDF5.
ExpressionAtlasiP43026. baseline and differential.
GenevestigatoriP43026.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of recombinant human growth/differentiation factor 5."
    Hoetten G., Neidhardt H., Jacobowsky B., Pohl J.
    Biochem. Biophys. Res. Commun. 204:646-652(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  2. "Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development."
    Chang S., Hoang B., Thomas J.T., Vukicevic S., Luyten F.P., Ryba N.J.P., Kozak C.A., Reddi A.H., Moos M.
    J. Biol. Chem. 269:28227-28234(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-276.
    Tissue: Articular cartilage.
  3. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-276.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  6. Cited for: FUNCTION, IDENTIFICATION AS LPS RECEPTOR, INTERACTION WITH CXCR4; HSP90AA1 AND HSPA8, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. "Cartilage-derived morphogenetic protein-1 promotes the differentiation of mesenchymal stem cells into chondrocytes."
    Bai X., Xiao Z., Pan Y., Hu J., Pohl J., Wen J., Li L.
    Biochem. Biophys. Res. Commun. 325:453-460(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. Cited for: INTERACTION WITH NOG, FUNCTION, VARIANTS SYNS2 LYS-445 AND THR-445, CHARACTERIZATION OF VARIANT SYNS2 THR-445.
  9. "New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance."
    Schwaerzer G.K., Hiepen C., Schrewe H., Nickel J., Ploeger F., Sebald W., Mueller T., Knaus P.
    J. Bone Miner. Res. 27:429-442(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BMPR2; NOG; BMPR1A AND BMPR1B, FUNCTION, VARIANT BDA2 PRO-441, VARIANT SYNS2 ASN-475, CHARACTERIZATION OF VARIANT SYNS2 ASN-475, CHARACTERIZATION OF VARIANT BDA2 PRO-441.
  10. Cited for: INTERACTION WITH NOG; BMPR1B AND BMPR1A, FUNCTION, VARIANT SYNS2 ARG-414, CHARACTERIZATION OF VARIANT SYNS2 ARG-414, VARIANT BDA1C ARG-414, CHARACTERIZATION OF VARIANTS BDA1C CYS-399 AND ARG-414.
  11. "Molecular analysis of two novel missense mutations in the GDF5 proregion that reduce protein activity and are associated with brachydactyly type C."
    Stange K., Thieme T., Hertel K., Kuhfahl S., Janecke A.R., Piza-Katzer H., Penttinen M., Hietala M., Dathe K., Mundlos S., Schwarz E., Seemann P.
    J. Mol. Biol. 426:3221-3231(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, VARIANTS BDC PRO-201 AND PRO-263, CHARACTERIZATION OF VARIANTS BDC PRO-201 AND PRO-263.
  12. "A novel mutation in CDMP1 causes brachydactyly type C with 'angel-shaped phalanx'. A genotype-phenotype correlation in the mutational spectrum."
    Gutierrez-Amavizca B.E., Brambila-Tapia A.J., Juarez-Vazquez C.I., Holder-Espinasse M., Manouvrier-Hanu S., Escande F., Barros-Nunez P.
    Eur. J. Med. Genet. 55:611-614(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN BDC.
  13. "Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity."
    Kotzsch A., Nickel J., Seher A., Sebald W., Muller T.D.
    EMBO J. 28:937-947(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 387-501 IN COMPLEX WITH MOUSE BMPR1B, FUNCTION, DISULFIDE BONDS.
  14. "Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1."
    Thomas J.T., Kilpatrick M.W., Lin K., Erlacher L., Lembessis P., Costa T., Tsipouras P., Luyten F.P.
    Nat. Genet. 17:58-64(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AMDG TYR-400.
  15. "Multiple synostosis type 2 (SYNS2) maps to 20q11.2 and caused by a missense mutation in the growth/differentiation factor 5 (GDF5)."
    Akarsu A.N., Rezaie T., Demirtas M., Farhud D.D., Sarfarazi M.
    Am. J. Hum. Genet. 65:A281-A281(1999)
    Cited for: VARIANT SYNS2 ASN-475.
  16. "Mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene in a kindred affected with fibular hypoplasia and complex brachydactyly (DuPan syndrome)."
    Faiyaz-Ul-Haque M., Ahmad W., Zaidi S.H.E., Haque S., Teebi A.S., Ahmad M., Cohn D.H., Tsui L.-C.
    Clin. Genet. 61:454-458(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DPS PRO-441.
  17. "Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1."
    Schwabe G.C., Tuerkmen S., Leschik G., Palanduz S., Stoever B., Goecke T.O., Mundlos S.
    Am. J. Med. Genet. A 124:356-363(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT BDC VAL-173.
  18. "Du Pan syndrome phenotype caused by heterozygous pathogenic mutations in CDMP1 gene."
    Szczaluba K., Hilbert K., Obersztyn E., Zabel B., Mazurczak T., Kozlowski K.
    Am. J. Med. Genet. A 138:379-383(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS DPS LEU-437 DEL; THR-439 AND LEU-440.
  19. "Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2."
    Seemann P., Schwappacher R., Kjaer K.W., Krakow D., Lehmann K., Dawson K., Stricker S., Pohl J., Ploeger F., Staub E., Nickel J., Sebald W., Knaus P., Mundlos S.
    J. Clin. Invest. 115:2373-2381(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SYM1B LEU-438, VARIANT BDA2 PRO-441, CHARACTERIZATION OF VARIANT SYM1B LEU-438, CHARACTERIZATION OF VARIANT BDA2 PRO-441.
  20. Cited for: VARIANT SYNS2 LEU-438.
  21. "A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families."
    Wang X., Xiao F., Yang Q., Liang B., Tang Z., Jiang L., Zhu Q., Chang W., Jiang J., Jiang C., Ren X., Liu J.-Y., Wang Q.K., Liu M.
    Am. J. Med. Genet. A 140:1846-1853(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SYM1B LYS-491.
  22. "A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis."
    Miyamoto Y., Mabuchi A., Shi D., Kubo T., Takatori Y., Saito S., Fujioka M., Sudo A., Uchida A., Yamamoto S., Ozaki K., Takigawa M., Tanaka T., Nakamura Y., Jiang Q., Ikegawa S.
    Nat. Genet. 39:529-533(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO OSTEOARTHRITIS TYPE 5.
  23. "Compound heterozygosity for GDF5 in Du Pan type chondrodysplasia."
    Douzgou S., Lehmann K., Mingarelli R., Mundlos S., Dallapiccola B.
    Am. J. Med. Genet. A 146:2116-2121(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS DPS GLN-378 AND THR-436.
  24. Cited for: VARIANT BDA2 GLN-380, CHARACTERIZATION OF VARIANT BDA2 GLN-380.
  25. "Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism."
    Yang W., Cao L., Liu W., Jiang L., Sun M., Zhang D., Wang S., Lo W.H., Luo Y., Zhang X.
    J. Hum. Genet. 53:368-374(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SYM1B ARG-373, CHARACTERIZATION OF VARIANT SYM1B ARG-373.
  26. Cited for: VARIANT BDA1C CYS-399, CHARACTERIZATION OF VARIANT BDA1C CYS-399.

Entry informationi

Entry nameiGDF5_HUMAN
AccessioniPrimary (citable) accession number: P43026
Secondary accession number(s): E1P5Q2, Q96SB1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2002
Last modified: May 27, 2015
This is version 164 of the entry and version 3 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.