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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-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
  • 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

BioCyciZFISH:ENSG00000125965-MONOMER.
ReactomeiR-HSA-2129379. 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
Proteomesi
  • UP000005640 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_017407400C → Y in AMDG. 1 Publication1
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.
See also OMIM:201250
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.
See also OMIM:113100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037978173M → V in BDC. 1 PublicationCorresponds to variant rs28936397dbSNPEnsembl.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.
See also OMIM:228900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054910378R → Q in DPS. 1 Publication1
Natural variantiVAR_054911436P → T in DPS. 1 Publication1
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 rs28936683dbSNPEnsembl.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.
See also OMIM:615298
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 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 Publications1
Natural variantiVAR_037983491E → K in SYM1B. 1 Publication1
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)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 Publications1
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 rs28936683dbSNPEnsembl.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 Publications1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_046743380R → Q in BDA2; reduces activity; impairs processing. 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 rs28936683dbSNPEnsembl.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.
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. BDA1C inheritance can be autosomal dominant or autosomal recessive. Autosomal dominant BDA1C has a milder phenotype.
See also OMIM:615072
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 Publications1
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
Mutagenesisi490Y → N: Resitant to NOG inhibition. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi8200.
MalaCardsiGDF5.
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.

Chemistry databases

DrugBankiDB02325. Isopropyl Alcohol.

Polymorphism and mutation databases

BioMutaiGDF5.
DMDMi20141384.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
PropeptideiPRO_000003391228 – 381Sequence analysisAdd BLAST354
ChainiPRO_0000033913382 – 501Growth/differentiation factor 5Add BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi189N-linked (GlcNAc...)Sequence analysis1
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

EPDiP43026.
PaxDbiP43026.
PRIDEiP43026.

PTM databases

iPTMnetiP43026.
PhosphoSitePlusiP43026.
SwissPalmiP43026.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000125965.
CleanExiHS_GDF5.
ExpressionAtlasiP43026. baseline and differential.
GenevisibleiP43026. HS.

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. Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631).By similarity6 Publications

Binary interactionsi

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

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi113839. 27 interactors.
DIPiDIP-5823N.
IntActiP43026. 4 interactors.
MINTiMINT-7264433.
STRINGi9606.ENSP00000363489.

Structurei

Secondary structure

1501
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi399 – 403Combined sources5
Beta strandi406 – 408Combined sources3
Helixi410 – 412Combined sources3
Helixi414 – 416Combined sources3
Beta strandi418 – 420Combined sources3
Beta strandi422 – 425Combined sources4
Beta strandi428 – 432Combined sources5
Helixi439 – 441Combined sources3
Helixi445 – 456Combined sources12
Turni458 – 460Combined sources3
Beta strandi466 – 479Combined sources14
Beta strandi481 – 483Combined sources3
Beta strandi485 – 500Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
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[»]
ProteinModelPortaliP43026.
SMRiP43026.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43026.

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43026.
KOiK04664.
OrthoDBiEOG091G09KP.
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. 2 hits.
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)DescriptionActionsGraphical viewLength
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 rs34534075dbSNPEnsembl.1
Natural variantiVAR_037978173M → V in BDC. 1 PublicationCorresponds to variant rs28936397dbSNPEnsembl.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 → A.2 PublicationsCorresponds to variant rs224331dbSNPEnsembl.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 Publication1
Natural variantiVAR_054910378R → Q in DPS. 1 Publication1
Natural variantiVAR_046743380R → Q in BDA2; reduces activity; impairs processing. 1 Publication1
Natural variantiVAR_064416399R → C in BDA1C; less effective than wild-type in stimulating chondrogenesis; impairs BMP signaling through BMPR1A. 2 Publications1
Natural variantiVAR_017407400C → Y in AMDG. 1 Publication1
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 Publication1
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 Publications1
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 rs28936683dbSNPEnsembl.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 Publications1
Natural variantiVAR_074162486V → M in BDC. 1 Publication1
Natural variantiVAR_037983491E → K in SYM1B. 1 Publication1

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.
UniGeneiHs.1573.

Genome annotation databases

EnsembliENST00000374369; ENSP00000363489; ENSG00000125965.
ENST00000374372; ENSP00000363492; ENSG00000125965.
GeneIDi8200.
KEGGihsa:8200.
UCSCiuc002xck.2. 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.
NP_001306067.1. NM_001319138.1.
XP_011527377.1. XM_011529075.2.
UniGeneiHs.1573.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
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[»]
ProteinModelPortaliP43026.
SMRiP43026.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113839. 27 interactors.
DIPiDIP-5823N.
IntActiP43026. 4 interactors.
MINTiMINT-7264433.
STRINGi9606.ENSP00000363489.

Chemistry databases

DrugBankiDB02325. Isopropyl Alcohol.

PTM databases

iPTMnetiP43026.
PhosphoSitePlusiP43026.
SwissPalmiP43026.

Polymorphism and mutation databases

BioMutaiGDF5.
DMDMi20141384.

Proteomic databases

EPDiP43026.
PaxDbiP43026.
PRIDEiP43026.

Protocols and materials databases

DNASUi8200.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8200.
DisGeNETi8200.
GeneCardsiGDF5.
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-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

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43026.
KOiK04664.
OrthoDBiEOG091G09KP.
PhylomeDBiP43026.
TreeFamiTF316134.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125965-MONOMER.
ReactomeiR-HSA-2129379. Molecules associated with elastic fibres.
SignaLinkiP43026.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000125965.
CleanExiHS_GDF5.
ExpressionAtlasiP43026. baseline and differential.
GenevisibleiP43026. HS.

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. 2 hits.
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...

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: November 2, 2016
This is version 180 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

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 one 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.