Q13253 (NOGG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Noggin

Gene names

Name:

NOG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	232 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 syndrome (SYM1) [MIM:185800]: Characterized by the hereditary absence of the proximal interphalangeal (PIP) joints (Cushing symphalangism). Severity of PIP joint involvement diminishes towards the radial side. 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. Conducive 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.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 process	Chondrogenesis Differentiation
Cellular component	Secreted
Disease	Deafness Disease mutation
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Traceable author statement. Source: Reactome axial mesoderm development Inferred from electronic annotation. Source: Compara 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: Compara 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 endoderm formation Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB face morphogenesis Inferred from electronic annotation. Source: Compara 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: Compara lung morphogenesis Inferred from electronic annotation. Source: Compara mesoderm formation Inferred from electronic annotation. Source: Compara middle ear morphogenesis Inferred from mutant phenotype Ref.4. Source: BHF-UCL motor neuron axon guidance Inferred from electronic annotation. Source: Compara negative regulation of BMP signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of canonical Wnt receptor 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: Compara 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: Compara neural plate morphogenesis Inferred from electronic annotation. Source: Compara neural tube closure Inferred from electronic annotation. Source: Compara notochord morphogenesis Inferred from electronic annotation. Source: Compara osteoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB pituitary gland development Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara prostatic bud formation Inferred from electronic annotation. Source: Compara 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 somatic stem cell maintenance Inferred from mutant phenotype PubMed 17889703. Source: BHF-UCL somite development Inferred from electronic annotation. Source: Compara spinal cord development Inferred from electronic annotation. Source: Compara ureteric bud formation Inferred from electronic annotation. Source: Compara wound healing Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	extracellular space Inferred from direct assay PubMed 11562478Ref.1. Source: BHF-UCL
Molecular_function	protein homodimerization activity Inferred from direct assay PubMed 11562478. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BMP7	P18075	1	EBI-1035205,EBI-1035195

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Potential

Chain

28 – 232

205

Noggin

PRO_0000019813

Amino acid modifications

Glycosylation

62

1

N-linked (GlcNAc...) Potential

Disulfide bond

155 ↔ 192

Ref.3

Disulfide bond

178 ↔ 228

Ref.3

Disulfide bond

184 ↔ 230

Ref.3

Disulfide bond

207 ↔ 215

Ref.3

Natural variations

Natural variant

35

1

P → A in BDB2. Ref.10

VAR_036997

Natural variant

35

1

P → R in SYM1 and TCC. Ref.4 Ref.6

VAR_011361

Natural variant

35

1

P → S in SYM1 and BDB2. Ref.8 Ref.10
Corresponds to variant rs28937580 [ dbSNP | Ensembl ].

VAR_018324

Natural variant

36

1

A → P in BDB2. Ref.10

VAR_036998

Natural variant

48

1

E → K in BDB2. Ref.10

VAR_036999

Natural variant

167

1

R → G in BDB2. Ref.10

VAR_037000

Natural variant

184

1

C → Y in SYM1; sporadic; de novo mutation. Ref.5

VAR_018325

Natural variant

187

1

P → S in BDB2. Ref.10

VAR_037001

Natural variant

189

1

G → C in SYM1. Ref.4

VAR_011362

Natural variant

204

1

R → L in TCC. Ref.6

VAR_018326

Natural variant

205

1

W → C in SYM1. Ref.9

VAR_037605

Natural variant

217

1

W → G in SYNS1. Ref.4

VAR_011363

Natural variant

220

1

I → N in SYM1. Ref.4

VAR_011364

Natural variant

222

1

Y → C in SYM1 and TCC. Ref.4 Ref.6

VAR_011365

Natural variant

222

1

Y → D in SYM1. Ref.4

VAR_011366

Natural variant

223

1

P → L in SYM1. Ref.4

VAR_011367

Natural variant

232

1

C → W in SYNS1. Ref.11

VAR_064541

Secondary structure

1

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232

Helix Strand Turn

Details...

Beta strand

29 – 32

4

Helix

58 – 60

3

Helix

63 – 70

8

Helix

71 – 73

3

Turn

76 – 78

3

Beta strand

79 – 82

4

Helix

99 – 109

11

Helix

118 – 121

4

Beta strand

129 – 131

3

Helix

139 – 153

15

Beta strand

158 – 163

6

Beta strand

168 – 177

10

Beta strand

185 – 188

4

Beta strand

191 – 207

17

Helix

210 – 212

3

Beta strand

214 – 231

18

Sequences

	Sequence		Length	Mass (Da)
	Q13253 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: FCA0D8E1E2098580	FASTA	232	25,774
	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

References

	« Hide 'large scale' referencesShow '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 SYM1/SYNS1 ARG-35; CYS-189; GLY-217; ASN-220; CYS-222; ASP-222 AND LEU-223.
[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 SYM1 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 SYM1 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 SYM1 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

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U31202 Genomic DNA. Translation: AAA83259.1.
BC034027 mRNA. Translation: AAH34027.1.

IPI

IPI00012361.

RefSeq

NP_005441.1. NM_005450.4.

UniGene

Hs.248201.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M4U	X-ray	2.42	A	28-232	[»]

ProteinModelPortal

Q13253.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13253. 1 interaction.

MINT

MINT-3027418.

STRING

9606.ENSP00000328181.

PTM databases

PhosphoSite

Q13253.

Polymorphism databases

DMDM

15214099.

Proteomic databases

PaxDb

Q13253.

PRIDE

Q13253.

Protocols and materials databases

DNASU

9241.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000332822; ENSP00000328181; ENSG00000183691.

GeneID

9241.

KEGG

hsa:9241.

UCSC

uc002iup.2. human.

Organism-specific databases

CTD

9241.

GeneCards

GC17P054671.

HGNC

HGNC:7866. NOG.

HPA

CAB011490.

MIM

184460. phenotype.
185800. phenotype.
186500. phenotype.
186570. phenotype.
602991. gene.
611377. phenotype.

neXtProt

NX_Q13253.

Orphanet

140908. Brachydactyly type B2.
3237. Multiple synostoses syndrome.
3250. Proximal symphalangism.
140917. Stapes ankylosis with broad thumbs and toes.
1412. Tarsal-carpal coalition syndrome.

PharmGKB

PA31670.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42124.

HOGENOM

HOG000089944.

HOVERGEN

HBG006514.

InParanoid

Q13253.

KO

K04658.

OMA

RFWPRFV.

OrthoDB

EOG4QNMX6.

PhylomeDB

Q13253.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Bgee

Q13253.

CleanEx

HS_NOG.

Genevestigator

Q13253.

GermOnline

ENSG00000183691. Homo sapiens.

Family and domain databases

InterPro

IPR008717. Noggin.
[Graphical view]

PANTHER

PTHR10494. PTHR10494. 1 hit.

Pfam

PF05806. Noggin. 1 hit.
[Graphical view]

PIRSF

PIRSF008129. Noggin. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q13253.

GenomeRNAi

9241.

NextBio

34645.

SOURCE

Search...

Entry information

Entry name

NOGG_HUMAN

Accession

Primary (citable) accession number: Q13253

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 14, 2001
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.