Q9UK05 (GDF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth/differentiation factor 2
Short name=GDF-2

Alternative name(s):
Bone morphogenetic protein 9
Short name=BMP-9

Gene names

Name:	GDF2
Synonyms:	BMP9

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	429 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	Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks. Ref.6 Ref.7
Subunit structure	Homodimer; disulfide-linked. Ref.8 Ref.9
Subcellular location	Secreted Ref.6.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Biological process	Angiogenesis
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from direct assay PubMed 17068149. Source: BHF-UCL activin receptor signaling pathway Inferred from direct assay PubMed 17068149. Source: BHF-UCL cartilage development Traceable author statement PubMed 20406889. Source: DFLAT cellular iron ion homeostasis Traceable author statement PubMed 20406889. Source: DFLAT growth Inferred from electronic annotation. Source: InterPro negative regulation of DNA biosynthetic process Inferred from direct assay PubMed 19366699. Source: BHF-UCL negative regulation of DNA replication Traceable author statement PubMed 20406889. Source: DFLAT negative regulation of angiogenesis Traceable author statement PubMed 20406889. Source: DFLAT negative regulation of blood vessel endothelial cell migration Traceable author statement PubMed 20406889. Source: DFLAT negative regulation of cell growth Inferred from direct assay PubMed 17068149. Source: BHF-UCL negative regulation of endothelial cell proliferation Inferred from direct assay PubMed 20406889. Source: DFLAT ossification Traceable author statement PubMed 20406889. Source: DFLAT osteoblast differentiation Inferred from electronic annotation. Source: Compara pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 17068149. Source: BHF-UCL patterning of blood vessels Inferred from direct assay PubMed 20406889. Source: DFLAT positive regulation of BMP signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of angiogenesis Inferred from direct assay PubMed 20406889. Source: DFLAT positive regulation of endothelial cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell proliferation Inferred from direct assay PubMed 20406889. Source: DFLAT positive regulation of interleukin-8 production Inferred from direct assay PubMed 19366699. Source: BHF-UCL positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 17068149PubMed 19366699PubMed 19903896. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19366699. Source: BHF-UCL vasculogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Propeptide

23 – 319

297

By similarity

PRO_0000033902

Chain

320 – 429

110

Growth/differentiation factor 2

PRO_0000033903

Amino acid modifications

Glycosylation

71

1

N-linked (GlcNAc...) Potential

Glycosylation

136

1

N-linked (GlcNAc...) Potential

Disulfide bond

327 ↔ 393

Ref.8 Ref.9

Disulfide bond

356 ↔ 426

Ref.8 Ref.9

Disulfide bond

360 ↔ 428

Ref.8 Ref.9

Disulfide bond

392

Interchain Ref.8 Ref.9

Secondary structure

1

.

.

.

.

.

.

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.

.

.

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.

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.

.

.

.

.

429

Helix Strand Turn

Details...

Beta strand

326 – 335

10

Turn

336 – 340

5

Turn

342 – 344

3

Beta strand

345 – 347

3

Beta strand

349 – 359

11

Helix

366 – 368

3

Helix

372 – 383

12

Turn

385 – 387

3

Beta strand

393 – 406

14

Beta strand

412 – 428

17

Sequences

	Sequence		Length	Mass (Da)
	Q9UK05 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 5AC15DCA205FF086	FASTA	429	47,320
	10 20 30 40 50 60 MCPGALWVAL PLLSLLAGSL QGKPLQSWGR GSAGGNAHSP LGVPGGGLPE HTFNLKMFLE 70 80 90 100 110 120 NVKVDFLRSL NLSGVPSQDK TRVEPPQYMI DLYNRYTSDK STTPASNIVR SFSMEDAISI 130 140 150 160 170 180 TATEDFPFQK HILLFNISIP RHEQITRAEL RLYVSCQNHV DPSHDLKGSV VIYDVLDGTD 190 200 210 220 230 240 AWDSATETKT FLVSQDIQDE GWETLEVSSA VKRWVRSDST KSKNKLEVTV ESHRKGCDTL 250 260 270 280 290 300 DISVPPGSRN LPFFVVFSND HSSGTKETRL ELREMISHEQ ESVLKKLSKD GSTEAGESSH 310 320 330 340 350 360 EEDTDGHVAA GSTLARRKRS AGAGSHCQKT SLRVNFEDIG WDSWIIAPKE YEAYECKGGC 370 380 390 400 410 420 FFPLADDVTP TKHAIVQTLV HLKFPTKVGK ACCVPTKLSP ISVLYKDDMG VPTLKYHYEG MSVAECGCR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Celeste A.J. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"Growth/differentiation factor-2, a new TGF-beta family member with bone promoting activities." Zimmers T.A., Koniaris L.G., Sitzmann J.V., Lee S.-J. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 316-429. Tissue: Liver.
[6]	"Bone morphogenetic protein-9 is a circulating vascular quiescence factor." David L., Mallet C., Keramidas M., Lamande N., Gasc J.M., Dupuis-Girod S., Plauchu H., Feige J.J., Bailly S. Circ. Res. 102:914-922(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties." Mahlawat P., Ilangovan U., Biswas T., Sun L.Z., Hinck A.P. Biochemistry 51:6328-6341(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ACVRL1.
[8]	"Crystal structure of BMP-9 and functional interactions with pro-region and receptors." Brown M.A., Zhao Q., Baker K.A., Naik C., Chen C., Pukac L., Singh M., Tsareva T., Parice Y., Mahoney A., Roschke V., Sanyal I., Choe S. J. Biol. Chem. 280:25111-25118(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF 320-429, DISULFIDE BONDS.
[9]	"Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex." Townson S.A., Martinez-Hackert E., Greppi C., Lowden P., Sako D., Liu J., Ucran J.A., Liharska K., Underwood K.W., Seehra J., Kumar R., Grinberg A.V. J. Biol. Chem. 287:27313-27325(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.36 ANGSTROMS) OF 320-429 IN COMPLEX WITH ACVRL1 AND ACVR2B, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

Wikipedia

GDF2 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF188285 mRNA. Translation: AAD56960.1.
AL731561 Genomic DNA. Translation: CAH74046.1.
CH471251 Genomic DNA. Translation: EAW50660.1.
BC069643 mRNA. Translation: AAH69643.1.
BC074921 mRNA. Translation: AAH74921.1.
AF156891 mRNA. Translation: AAD40309.1.

IPI

IPI00007015.

RefSeq

NP_057288.1. NM_016204.1.

UniGene

Hs.279463.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZKZ	X-ray	2.33	A	320-429	[»]
4FAO	X-ray	3.36	A/B/G/H/M/N/S/T/a/b/g/h	320-429	[»]

ProteinModelPortal

Q9UK05.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000249598.

PTM databases

PhosphoSite

Q9UK05.

Polymorphism databases

DMDM

13124266.

Proteomic databases

PaxDb

Q9UK05.

PRIDE

Q9UK05.

Protocols and materials databases

DNASU

2658.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000249598; ENSP00000249598; ENSG00000128802.
ENST00000581492; ENSP00000463051; ENSG00000263761.

GeneID

2658.

KEGG

hsa:2658.

UCSC

uc001jfa.1. human.

Organism-specific databases

CTD

2658.

GeneCards

GC10M048413.

HGNC

HGNC:4217. GDF2.

HPA

CAB023357.

MIM

605120. gene.

neXtProt

NX_Q9UK05.

PharmGKB

PA28632.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG280573.

HOGENOM

HOG000249477.

HOVERGEN

HBG106648.

InParanoid

Q9UK05.

KO

K05503.

OMA

ENMKVDF.

OrthoDB

EOG48WC29.

PhylomeDB

Q9UK05.

Gene expression databases

Bgee

Q9UK05.

CleanEx

HS_GDF2.

Genevestigator

Q9UK05.

GermOnline

ENSG00000128802. Homo sapiens.

Family and domain databases

InterPro

IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]

PANTHER

PTHR11848. PTHR11848. 1 hit.

Pfam

PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]

PRINTS

PR00669. INHIBINA.

SMART

SM00204. TGFB. 1 hit.
[Graphical view]

PROSITE

PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UK05.

GenomeRNAi

2658.

NextBio

10496.

SOURCE

Search...

Entry information

Entry name

GDF2_HUMAN

Accession

Primary (citable) accession number: Q9UK05
Secondary accession number(s): Q5VSQ9, Q9Y571

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 111 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.