Reviewed, UniProtKB/Swiss-Prot Q13253 (NOGG_HUMAN)

Names and origin

Protein names

Recommended name:
    Noggin

Gene names

Name:

NOG

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 By similarity.
Subunit structure	Homodimer; disulfide-linked By similarity.
Subcellular location	Secreted.
Involvement in disease	Defects in NOG are a cause of symphalangism proximal syndrome (SYM1) [MIM:185800]. SYM1 is 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. Ref.3 Ref.4 Ref.6 Ref.7 Ref.8 Defects in NOG are the cause of multiple synostoses syndrome 1 (SYNS1) [MIM:186500]; also known as synostoses, multiple, with brachydactyly/symphalangism-brachydactyly syndrome. SYNS1 is characterized by tubular-shaped (hemicylindrical) nose with lack of alar flare, otosclerotic deafness, and multiple progressive joint fusions commencing in the hand. The joint fusions are progressive, commencing in the fifth proximal interphalangeal joint in early childhood (or at birth in some individuals) and progressing in an ulnar-to-radial and proximal-to-distal direction. With increasing age, ankylosis of other joints, including the cervical vertebrae, hips, and humeroradial joints, develop. Ref.6 Defects in NOG are the cause of tarsal-carpal coalition syndrome (TCC) [MIM:186570]. TCC is an 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. Ref.6 Ref.5 Defects in NOG are a cause of stapes ankylosis with broad thumb and toes [MIM:184460]. Stapes ankylosis with broad thumb and toes is a 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. Ref.6 Defects in NOG are the cause of brachydactyly type B2 (BDB2) [MIM:611377]. BDB2 is a subtype of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones, and partial cutaneous syndactyly. Ref.6 Ref.9
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
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from Experiment. Source: Reactome cartilage development Inferred from electronic annotation. Source: UniProtKB-KW dorsal/ventral pattern formation Ref.1 Inferred from direct assay. Source: UniProtKB embryonic digit morphogenesis Ref.3 Inferred from mutant phenotype. Source: UniProtKB embryonic skeletal joint morphogenesis Inferred from mutant phenotype. Source: UniProtKB epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB middle ear morphogenesis Ref.3 Inferred from mutant phenotype. Source: UniProtKB negative regulation of BMP signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cardiac muscle cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cytokine activity Inferred from physical interaction. Source: UniProtKB osteoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW somatic stem cell maintenance Inferred from mutant phenotype. Source: UniProtKB wound healing Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	extracellular space Ref.1 Ref.3 Inferred from direct assay. Source: UniProtKB
Molecular function	cytokine binding Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB
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

Natural variations

Natural variant

35

1

P → A in BDB2. Ref.9

VAR_036997

Natural variant

35

1

P → R in SYM1 and TCC.

VAR_011361

Natural variant

35

1

P → S in SYM1 and BDB2. dbSNP rs28937580.

VAR_018324

Natural variant

36

1

A → P in BDB2. Ref.9

VAR_036998

Natural variant

48

1

E → K in BDB2. Ref.9

VAR_036999

Natural variant

167

1

R → G in BDB2. Ref.9

VAR_037000

Natural variant

184

1

C → Y in SYM1; sporadic; de novo mutation. Ref.4

VAR_018325

Natural variant

187

1

P → S in BDB2. Ref.9

VAR_037001

Natural variant

189

1

G → C in SYM1. Ref.3

VAR_011362

Natural variant

204

1

R → L in TCC. Ref.5

VAR_018326

Natural variant

205

1

W → C in SYM1. Ref.8

VAR_037605

Natural variant

217

1

W → G in SYNS1.

VAR_011363

Natural variant

220

1

I → N in SYM1. Ref.3

VAR_011364

Natural variant

222

1

Y → C in SYM1 and TCC.

VAR_011365

Natural variant

222

1

Y → D in SYM1. Ref.3

VAR_011366

Natural variant

223

1

P → L in SYM1. Ref.3

VAR_011367

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)
	Q13253-1 [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: 7666191] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[3]	"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: 10080184] [Abstract] Cited for: VARIANTS SYM1/SYNS1 ARG-35; CYS-189; GLY-217; ASN-220; CYS-222; ASP-222 AND LEU-223.
[4]	"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: 11846737] [Abstract] Cited for: VARIANT SYM1 TYR-184.
[5]	"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: 11545688] [Abstract] Cited for: VARIANTS TCC ARG-35; LEU-204 AND CYS-222.
[6]	"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: 12089654] [Abstract] Cited for: DISEASE.
[7]	"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: 11857750] [Abstract] Cited for: VARIANT SYM1 SER-35.
[8]	"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: 15770128] [Abstract] Cited for: VARIANT SYM1 CYS-205.
[9]	"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: 17668388] [Abstract] Cited for: VARIANTS BDB2 ALA-35; SER-35; PRO-36; LYS-48; GLY-167 AND SER-187.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

IPI

IPI00012361.

RefSeq

NP_005441.1.

UniGene

Hs.248201

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13253. 1 interaction.

Proteomic databases

PRIDE

Q13253.

Genome annotation databases

Ensembl

ENSG00000183691. Homo sapiens. [Contig view]

GeneID

9241.

KEGG

hsa:9241.

UCSC

uc002iup.2. human.

Organism-specific databases

GeneCards

GC17P052026.

H-InvDB

HIX0014011.

HGNC

HGNC:7866. NOG.

HPA

CAB011490.

MIM

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

Orphanet

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

PharmGKB

PA134864904.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q13253.

HOVERGEN

Q13253.

OMA

Q13253. TILRWRC.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.

Reactome

REACT_12034. Signaling by BMP.

Gene expression databases

ArrayExpress

Q13253.

Bgee

Q13253.

CleanEx

HS_NOG.

GermOnline

ENSG00000183691. Homo sapiens.

Family and domain databases

InterPro

IPR008717. Noggin.
[Graphical view]

PANTHER

PTHR10494. Noggin. 1 hit.

Pfam

PF05806. Noggin. 1 hit.
[Graphical view]

PIRSF

PIRSF008129. Noggin. 1 hit.

ProtoNet

Search...

Other Resources

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:	July 7, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)