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Protein

Growth/differentiation factor 3

Gene

GDF3

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

Functioni

Growth factor involved in early embryonic development and adipose-tissue homeostasis. During embryogenesis controls formation of anterior visceral endoderm and mesoderm and the establishment of anterior-posterior identity through a receptor complex comprising the receptor ACVR1B and the coreceptor TDGF1/Cripto (By similarity). Regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the receptor complex based on ACVR1C and TDGF1/Cripto (PubMed:21805089).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Developmental protein, Growth factor

Enzyme and pathway databases

BioCyciZFISH:G66-31351-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 3
Short name:
GDF-3
Gene namesi
Name:GDF3
ORF Names:UNQ222/PRO248
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:4218. GDF3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular space Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & Biotechi

Involvement in diseasei

Klippel-Feil syndrome 3, autosomal dominant (KFS3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement.
See also OMIM:613702
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065148266R → C in KFS3 and MCOPCB6; reduces the amount of active ligand secreted; reduced amout of mature protein in the cytosol. 1 PublicationCorresponds to variant rs140926412dbSNPEnsembl.1
Microphthalmia, isolated, with coloboma, 6 (MCOPCB6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).
See also OMIM:613703
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065148266R → C in KFS3 and MCOPCB6; reduces the amount of active ligand secreted; reduced amout of mature protein in the cytosol. 1 PublicationCorresponds to variant rs140926412dbSNPEnsembl.1
Natural variantiVAR_065149274R → W in MCOPCB6. 1 PublicationCorresponds to variant rs387906946dbSNPEnsembl.1
Microphthalmia, isolated, 7 (MCOP7)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
See also OMIM:613704
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065147195R → Q in MCOP7; reduces the amount of active ligand secreted. 1 PublicationCorresponds to variant rs146973734dbSNPEnsembl.1
Natural variantiVAR_065150305L → P in MCOP7; also detected in a patient with bilateral iris coloboma; reduces the amount of active ligand secreted. 1 PublicationCorresponds to variant rs387906945dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Microphthalmia

Organism-specific databases

DisGeNETi9573.
MalaCardsiGDF3.
MIMi613702. phenotype.
613703. phenotype.
613704. phenotype.
OpenTargetsiENSG00000184344.
Orphaneti98938. Colobomatous microphthalmia.
2542. Isolated anophthalmia - microphthalmia.
2345. Isolated Klippel-Feil syndrome.
PharmGKBiPA28633.

Polymorphism and mutation databases

BioMutaiGDF3.
DMDMi46397885.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PropeptideiPRO_000003390825 – 250Sequence analysisAdd BLAST226
ChainiPRO_0000033909251 – 364Growth/differentiation factor 3Add BLAST114

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi112N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi264 ↔ 329By similarity
Disulfide bondi293 ↔ 361By similarity
Disulfide bondi297 ↔ 363By similarity
Glycosylationi306N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Synthesized as large precursor molecule that undergo proteolytic cleavage, releasing the pro-domain from the active, receptor binding, C-terminal region of the molecule.Curated

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9NR23.
PaxDbiQ9NR23.
PeptideAtlasiQ9NR23.
PRIDEiQ9NR23.

PTM databases

PhosphoSitePlusiQ9NR23.

Expressioni

Gene expression databases

BgeeiENSG00000184344.
CleanExiHS_GDF3.
GenevisibleiQ9NR23. HS.

Organism-specific databases

HPAiHPA018468.

Interactioni

Subunit structurei

Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.Curated

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114942. 3 interactors.
STRINGi9606.ENSP00000331745.

Structurei

3D structure databases

ProteinModelPortaliQ9NR23.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00740000114888.
HOGENOMiHOG000249476.
HOVERGENiHBG004860.
InParanoidiQ9NR23.
KOiK05495.
OMAiANYCHGD.
OrthoDBiEOG091G0K7Z.
PhylomeDBiQ9NR23.
TreeFamiTF351789.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
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]
PRINTSiPR00669. INHIBINA.
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.

Q9NR23-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRFLPDLAF SFLLILALGQ AVQFQEYVFL QFLGLDKAPS PQKFQPVPYI
60 70 80 90 100
LKKIFQDREA AATTGVSRDL CYVKELGVRG NVLRFLPDQG FFLYPKKISQ
110 120 130 140 150
ASSCLQKLLY FNLSAIKERE QLTLAQLGLD LGPNSYYNLG PELELALFLV
160 170 180 190 200
QEPHVWGQTT PKPGKMFVLR SVPWPQGAVH FNLLDVAKDW NDNPRKNFGL
210 220 230 240 250
FLEILVKEDR DSGVNFQPED TCARLRCSLH ASLLVVTLNP DQCHPSRKRR
260 270 280 290 300
AAIPVPKLSC KNLCHRHQLF INFRDLGWHK WIIAPKGFMA NYCHGECPFS
310 320 330 340 350
LTISLNSSNY AFMQALMHAV DPEIPQAVCI PTKLSPISML YQDNNDNVIL
360
RHYEDMVVDE CGCG
Length:364
Mass (Da):41,387
Last modified:April 13, 2004 - v3
Checksum:iE0D2EA86E2B73A0B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065147195R → Q in MCOP7; reduces the amount of active ligand secreted. 1 PublicationCorresponds to variant rs146973734dbSNPEnsembl.1
Natural variantiVAR_052574213G → R.1 PublicationCorresponds to variant rs12819884dbSNPEnsembl.1
Natural variantiVAR_065148266R → C in KFS3 and MCOPCB6; reduces the amount of active ligand secreted; reduced amout of mature protein in the cytosol. 1 PublicationCorresponds to variant rs140926412dbSNPEnsembl.1
Natural variantiVAR_065149274R → W in MCOPCB6. 1 PublicationCorresponds to variant rs387906946dbSNPEnsembl.1
Natural variantiVAR_065150305L → P in MCOP7; also detected in a patient with bilateral iris coloboma; reduces the amount of active ligand secreted. 1 PublicationCorresponds to variant rs387906945dbSNPEnsembl.1
Natural variantiVAR_020064328V → L.Corresponds to variant rs2302516dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF263538 mRNA. Translation: AAF91389.1.
AY358875 mRNA. Translation: AAQ89234.1.
AC006927 Genomic DNA. No translation available.
BC030959 mRNA. Translation: AAH30959.1.
CCDSiCCDS8581.1.
RefSeqiNP_065685.1. NM_020634.2.
UniGeneiHs.86232.

Genome annotation databases

EnsembliENST00000329913; ENSP00000331745; ENSG00000184344.
GeneIDi9573.
KEGGihsa:9573.
UCSCiuc001qte.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

GDF3 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF263538 mRNA. Translation: AAF91389.1.
AY358875 mRNA. Translation: AAQ89234.1.
AC006927 Genomic DNA. No translation available.
BC030959 mRNA. Translation: AAH30959.1.
CCDSiCCDS8581.1.
RefSeqiNP_065685.1. NM_020634.2.
UniGeneiHs.86232.

3D structure databases

ProteinModelPortaliQ9NR23.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114942. 3 interactors.
STRINGi9606.ENSP00000331745.

PTM databases

PhosphoSitePlusiQ9NR23.

Polymorphism and mutation databases

BioMutaiGDF3.
DMDMi46397885.

Proteomic databases

EPDiQ9NR23.
PaxDbiQ9NR23.
PeptideAtlasiQ9NR23.
PRIDEiQ9NR23.

Protocols and materials databases

DNASUi9573.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329913; ENSP00000331745; ENSG00000184344.
GeneIDi9573.
KEGGihsa:9573.
UCSCiuc001qte.4. human.

Organism-specific databases

CTDi9573.
DisGeNETi9573.
GeneCardsiGDF3.
HGNCiHGNC:4218. GDF3.
HPAiHPA018468.
MalaCardsiGDF3.
MIMi606522. gene.
613702. phenotype.
613703. phenotype.
613704. phenotype.
neXtProtiNX_Q9NR23.
OpenTargetsiENSG00000184344.
Orphaneti98938. Colobomatous microphthalmia.
2542. Isolated anophthalmia - microphthalmia.
2345. Isolated Klippel-Feil syndrome.
PharmGKBiPA28633.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00740000114888.
HOGENOMiHOG000249476.
HOVERGENiHBG004860.
InParanoidiQ9NR23.
KOiK05495.
OMAiANYCHGD.
OrthoDBiEOG091G0K7Z.
PhylomeDBiQ9NR23.
TreeFamiTF351789.

Enzyme and pathway databases

BioCyciZFISH:G66-31351-MONOMER.

Miscellaneous databases

GeneWikiiGDF3.
GenomeRNAii9573.
PROiQ9NR23.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184344.
CleanExiHS_GDF3.
GenevisibleiQ9NR23. HS.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
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]
PRINTSiPR00669. INHIBINA.
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 nameiGDF3_HUMAN
AccessioniPrimary (citable) accession number: Q9NR23
Secondary accession number(s): Q8NEJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: April 13, 2004
Last modified: November 30, 2016
This is version 136 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

Miscellaneous

In contrast to other members of this family, cannot be disulfide-linked due to an atypical cysteine knot configuration, where the fourth cysteine is missing. This fourth cysteine is involved in an inter-molecular bridge to stabilize the active form of homodimeric or heterodimeric signaling molecules.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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. 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.