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Q13253 (NOGG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Noggin
Gene names
Name:NOG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length232 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Essential for cartilage morphogenesis and joint formation. Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite. Ref.3

Subunit structure

Homodimer. Ref.3

Subcellular location

Secreted.

Involvement in disease

Symphalangism, proximal 1A (SYM1A) [MIM:185800]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5 Ref.8 Ref.9

Multiple synostoses syndrome 1 (SYNS1) [MIM:186500]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.11

Tarsal-carpal coalition syndrome (TCC) [MIM:186570]: Autosomal dominant disorder characterized by fusion of the carpals, tarsals and phalanges, short first metacarpals causing brachydactyly, and humeroradial fusion. TCC is allelic to SYM1, and different mutations in NOG can result in either TCC or SYM1 in different families.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Stapes ankylosis with broad thumb and toes (SABTS) [MIM:184460]: Congenital autosomal dominant disorder that includes hyperopia, a hemicylindrical nose, broad thumbs, great toes, and other minor skeletal anomalies but lacked carpal and tarsal fusion and symphalangism.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Brachydactyly B2 (BDB2) [MIM:611377]: A form of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones and partial cutaneous syndactyly.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the noggin family.

Ontologies

Keywords
   Biological processChondrogenesis
Differentiation
   Cellular componentSecreted
   DiseaseDeafness
Disease mutation
   DomainSignal
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Traceable author statement. Source: Reactome

axial mesoderm development

Inferred from electronic annotation. Source: Ensembl

cartilage development

Inferred from electronic annotation. Source: UniProtKB-KW

cell differentiation in hindbrain

Inferred from mutant phenotype PubMed 8582276. Source: BHF-UCL

cellular response to BMP stimulus

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral pattern formation

Inferred from direct assay Ref.1. Source: BHF-UCL

embryonic digit morphogenesis

Inferred from mutant phenotype Ref.4. Source: BHF-UCL

embryonic skeletal joint morphogenesis

Inferred from mutant phenotype PubMed 16151340. Source: BHF-UCL

embryonic skeletal system development

Inferred from mutant phenotype Ref.4. Source: BHF-UCL

endoderm formation

Inferred from electronic annotation. Source: Ensembl

epithelial to mesenchymal transition

Inferred from sequence or structural similarity. Source: UniProtKB

face morphogenesis

Inferred from electronic annotation. Source: Ensembl

fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation

Inferred from mutant phenotype PubMed 8582276. Source: BHF-UCL

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

limb development

Inferred from mutant phenotype Ref.4. Source: BHF-UCL

lung morphogenesis

Inferred from electronic annotation. Source: Ensembl

mesoderm formation

Inferred from electronic annotation. Source: Ensembl

middle ear morphogenesis

Inferred from mutant phenotype Ref.4. Source: BHF-UCL

motor neuron axon guidance

Inferred from electronic annotation. Source: Ensembl

negative regulation of BMP signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of astrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 15539560. Source: BHF-UCL

negative regulation of cardiac muscle cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cartilage development

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell migration

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

negative regulation of cytokine activity

Inferred from physical interaction PubMed 8752214. Source: BHF-UCL

negative regulation of osteoblast differentiation

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

negative regulation of pathway-restricted SMAD protein phosphorylation

Inferred from direct assay PubMed 15539560. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

nervous system development

Traceable author statement Ref.1. Source: ProtInc

neural plate morphogenesis

Inferred from electronic annotation. Source: Ensembl

neural tube closure

Inferred from electronic annotation. Source: Ensembl

notochord morphogenesis

Inferred from electronic annotation. Source: Ensembl

osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

pituitary gland development

Inferred from electronic annotation. Source: Ensembl

positive regulation of branching involved in ureteric bud morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of glomerulus development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

prostatic bud formation

Inferred from electronic annotation. Source: Ensembl

regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation

Inferred from mutant phenotype PubMed 8582276. Source: BHF-UCL

skeletal system development

Traceable author statement Ref.4. Source: ProtInc

somatic stem cell maintenance

Inferred from mutant phenotype PubMed 17889703. Source: BHF-UCL

somite development

Inferred from electronic annotation. Source: Ensembl

spinal cord development

Inferred from electronic annotation. Source: Ensembl

ureteric bud formation

Inferred from electronic annotation. Source: Ensembl

wound healing

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 11562478Ref.1. Source: BHF-UCL

   Molecular_functioncytokine binding

Inferred from physical interaction PubMed 8752214. Source: BHF-UCL

protein homodimerization activity

Inferred from direct assay PubMed 11562478. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BMP2P126432EBI-1035205,EBI-1029262

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 232205Noggin
PRO_0000019813

Amino acid modifications

Glycosylation621N-linked (GlcNAc...) Potential
Disulfide bond155 ↔ 192 Ref.3
Disulfide bond178 ↔ 228 Ref.3
Disulfide bond184 ↔ 230 Ref.3
Disulfide bond207 ↔ 215 Ref.3

Natural variations

Natural variant351P → A in BDB2. Ref.10
VAR_036997
Natural variant351P → R in SYM1A and TCC. Ref.4 Ref.6
VAR_011361
Natural variant351P → S in SYM1A and BDB2. Ref.8 Ref.10
Corresponds to variant rs28937580 [ dbSNP | Ensembl ].
VAR_018324
Natural variant361A → P in BDB2. Ref.10
VAR_036998
Natural variant481E → K in BDB2. Ref.10
VAR_036999
Natural variant1671R → G in BDB2. Ref.10
VAR_037000
Natural variant1841C → Y in SYM1A; sporadic; de novo mutation. Ref.5
VAR_018325
Natural variant1871P → S in BDB2. Ref.10
VAR_037001
Natural variant1891G → C in SYM1A. Ref.4
VAR_011362
Natural variant2041R → L in TCC. Ref.6
VAR_018326
Natural variant2051W → C in SYM1A. Ref.9
VAR_037605
Natural variant2171W → G in SYNS1. Ref.4
VAR_011363
Natural variant2201I → N in SYM1A. Ref.4
VAR_011364
Natural variant2221Y → C in SYM1A and TCC. Ref.4 Ref.6
VAR_011365
Natural variant2221Y → D in SYM1A. Ref.4
VAR_011366
Natural variant2231P → L in SYM1A. Ref.4
VAR_011367
Natural variant2321C → W in SYNS1. Ref.11
VAR_064541

Secondary structure

............................... 232
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13253 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: FCA0D8E1E2098580

FASTA23225,774
        10         20         30         40         50         60 
MERCPSLGVT LYALVVVLGL RATPAGGQHY LHIRPAPSDN LPLVDLIEHP DPIFDPKEKD 

        70         80         90        100        110        120 
LNETLLRSLL GGHYDPGFMA TSPPEDRPGG GGGAAGGAED LAELDQLLRQ RPSGAMPSEI 

       130        140        150        160        170        180 
KGLEFSEGLA QGKKQRLSKK LRRKLQMWLW SQTFCPVLYA WNDLGSRFWP RYVKVGSCFS 

       190        200        210        220        230 
KRSCSVPEGM VCKPSKSVHL TVLRWRCQRR GGQRCGWIPI QYPIISECKC SC 

« Hide

References

« Hide 'large scale' references
[1]"Identification of mammalian noggin and its expression in the adult nervous system."
Valenzuela D.M., Economides A.N., Rojas E., Lamb T.M., Nunez L., Jones P., Ip N.Y., Espinosa R. III, Brannan C.I., Gilbert D.J., Copeland N.G., Jenkins N.A., Le Beau M.M., Harland R.M., Yancopoulos G.D.
J. Neurosci. 15:6077-6084(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta and Temporal cortex.
[2]"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: Prostate.
[3]"Structural basis of BMP signalling inhibition by the cystine knot protein Noggin."
Groppe J., Greenwald J., Wiater E., Rodriguez-Leon J., Economides A.N., Kwiatkowski W., Affolter M., Vale W.W., Belmonte J.C., Choe S.
Nature 420:636-642(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 28-232 IN COMPLEX WITH BMP7, FUNCTION, SUBUNIT, DISULFIDE BONDS.
[4]"Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis."
Gong Y., Krakow D., Marcelino J., Wilkin D., Chitayat D., Babul-Hirji R., Hudgins L., Cremers C.W., Cremers F.P.M., Brunner H.G., Reinker K., Rimoin D.L., Cohn D.H., Goodman F.R., Reardon W., Patton M., Francomano C.A., Warman M.L.
Nat. Genet. 21:302-304(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SYM1A ARG-35; CYS-189; ASN-220; CYS-222; ASP-222 AND LEU-223, VARIANT SYNS1 GLY-217.
[5]"Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome."
Takahashi T., Takahashi I., Komatsu M., Sawaishi Y., Higashi K., Nishimura G., Saito H., Takada G.
Clin. Genet. 60:447-451(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SYM1A TYR-184.
[6]"Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism."
Dixon M.E., Armstrong P., Stevens D.B., Bamshad M.
Genet. Med. 3:349-353(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TCC ARG-35; LEU-204 AND CYS-222.
[7]"Autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG, the gene encoding noggin."
Brown D.J., Kim T.B., Petty E.M., Downs C.A., Martin D.M., Strouse P.J., Moroi S.E., Milunsky J.M., Lesperance M.M.
Am. J. Hum. Genet. 71:618-624(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SABTS.
[8]"Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism."
Mangino M., Flex E., Digilio M.C., Giannotti A., Dallapiccola B.
Hum. Mutat. 19:308-308(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SYM1A SER-35.
[9]"The facio-audio-symphalangism syndrome in a four generation family with a nonsense mutation in the NOG-gene."
van den Ende J.J., Mattelaer P., Declau F., Vanhoenacker F., Claes J., Van Hul E., Baten E.
Clin. Dysmorphol. 14:73-80(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SYM1A CYS-205.
[10]"A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN."
Lehmann K., Seemann P., Silan F., Goecke T.O., Irgang S., Kjaer K.W., Kjaergaard S., Mahoney M.J., Morlot S., Reissner C., Kerr B., Wilkie A.O.M., Mundlos S.
Am. J. Hum. Genet. 81:388-396(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BDB2 ALA-35; SER-35; PRO-36; LYS-48; GLY-167 AND SER-187.
[11]"Facioaudiosymphalangism syndrome and growth acceleration associated with a heterozygous NOG mutation."
Rudnik-Schoneborn S., Takahashi T., Busse S., Schmidt T., Senderek J., Eggermann T., Zerres K.
Am. J. Med. Genet. A 152:1540-1544(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SYNS1 TRP-232.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U31202 Genomic DNA. Translation: AAA83259.1.
BC034027 mRNA. Translation: AAH34027.1.
RefSeqNP_005441.1. NM_005450.4.
UniGeneHs.248201.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M4UX-ray2.42A28-232[»]
ProteinModelPortalQ13253.
SMRQ13253. Positions 28-232.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114668. 2 interactions.
IntActQ13253. 2 interactions.
MINTMINT-3027418.
STRING9606.ENSP00000328181.

PTM databases

PhosphoSiteQ13253.

Polymorphism databases

DMDM15214099.

Proteomic databases

PaxDbQ13253.
PRIDEQ13253.

Protocols and materials databases

DNASU9241.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332822; ENSP00000328181; ENSG00000183691.
GeneID9241.
KEGGhsa:9241.
UCSCuc002iup.2. human.

Organism-specific databases

CTD9241.
GeneCardsGC17P054671.
HGNCHGNC:7866. NOG.
HPAHPA061318.
MIM184460. phenotype.
185800. phenotype.
186500. phenotype.
186570. phenotype.
602991. gene.
611377. phenotype.
neXtProtNX_Q13253.
Orphanet140908. Brachydactyly type B2.
3237. Multiple synostoses syndrome.
3250. Proximal symphalangism.
140917. Stapes ankylosis with broad thumbs and toes.
1412. Tarsal-carpal coalition syndrome.
PharmGKBPA31670.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42124.
HOGENOMHOG000089944.
HOVERGENHBG006514.
InParanoidQ13253.
KOK04658.
OMAAPGKKQR.
OrthoDBEOG7XSTFS.
PhylomeDBQ13253.
TreeFamTF353745.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ13253.
CleanExHS_NOG.
GenevestigatorQ13253.

Family and domain databases

InterProIPR008717. Noggin.
[Graphical view]
PANTHERPTHR10494. PTHR10494. 1 hit.
PfamPF05806. Noggin. 1 hit.
[Graphical view]
PIRSFPIRSF008129. Noggin. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ13253.
GeneWikiNoggin_(protein).
GenomeRNAi9241.
NextBio34645.
PROQ13253.
SOURCESearch...

Entry information

Entry nameNOGG_HUMAN
AccessionPrimary (citable) accession number: Q13253
Entry history
Integrated into UniProtKB/Swiss-Prot: August 14, 2001
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM