P61812 (TGFB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transforming growth factor beta-2
Short name=TGF-beta-2

Alternative name(s):
BSC-1 cell growth inhibitor
Cetermin
Glioblastoma-derived T-cell suppressor factor
Short name=G-TSF
Polyergin

Gene names

Name:

TGFB2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	414 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	TGF-beta 2 has suppressive effects on interleukin-2 dependent T-cell growth.
Subunit structure	Homodimer; disulfide-linked. Interacts with ASPN. Ref.11
Subcellular location	Secreted.
Involvement in disease	Note=A chromosomal aberration involving TGFB2 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Domain	Signal
Molecular function	Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	SMAD protein import into nucleus Inferred from direct assay. Source: BHF-UCL activation of protein kinase activity Inferred from direct assay. Source: BHF-UCL angiogenesis Traceable author statement. Source: UniProtKB cardiac epithelial to mesenchymal transition Inferred from direct assay. Source: BHF-UCL cardiac muscle cell proliferation Inferred from direct assay. Source: UniProtKB cardioblast differentiation Inferred from direct assay. Source: UniProtKB catagen Inferred from direct assay. Source: UniProtKB cell cycle arrest Inferred from direct assay. Source: BHF-UCL cell death Inferred from direct assay. Source: UniProtKB cell growth Inferred from electronic annotation. Source: InterPro cell-cell junction organization Inferred from direct assay. Source: BHF-UCL cell-cell signaling Traceable author statement. Source: ProtInc collagen fibril organization Inferred from direct assay. Source: BHF-UCL dopamine biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB embryonic digestive tract development Inferred from expression pattern. Source: DFLAT eye development Inferred from direct assay. Source: UniProtKB glial cell migration Inferred from direct assay. Source: BHF-UCL hair follicle morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB menstrual cycle phase Inferred from expression pattern. Source: BHF-UCL negative regulation of alkaline phosphatase activity Inferred from direct assay. Source: BHF-UCL negative regulation of cell growth Inferred from direct assay. Source: BHF-UCL negative regulation of epithelial cell proliferation Inferred from direct assay. Source: BHF-UCL negative regulation of immune response Traceable author statement. Source: UniProtKB negative regulation of macrophage cytokine production Inferred from direct assay. Source: DFLAT neuron development Inferred from sequence or structural similarity. Source: UniProtKB neutrophil chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB odontogenesis Non-traceable author statement. Source: BHF-UCL pathway-restricted SMAD protein phosphorylation Inferred from direct assay. Source: BHF-UCL platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome positive regulation of cardioblast differentiation Inferred from direct assay. Source: UniProtKB positive regulation of catagen Inferred from direct assay. Source: UniProtKB positive regulation of cell adhesion mediated by integrin Inferred from direct assay. Source: BHF-UCL positive regulation of cell cycle Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell growth Inferred from direct assay. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of epithelial cell migration Inferred from direct assay. Source: BHF-UCL positive regulation of epithelial to mesenchymal transition Inferred from direct assay. Source: BHF-UCL positive regulation of heart contraction Inferred from direct assay. Source: UniProtKB positive regulation of immune response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of integrin biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of neuron apoptosis Inferred from direct assay. Source: UniProtKB positive regulation of ossification Inferred from expression pattern. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from direct assay. Source: BHF-UCL positive regulation of protein secretion Inferred from direct assay. Source: BHF-UCL positive regulation of stress-activated MAPK cascade Inferred from direct assay. Source: BHF-UCL regulation of transforming growth factor beta2 production Inferred from mutant phenotype. Source: BHF-UCL response to hypoxia Inferred from mutant phenotype. Source: BHF-UCL response to progesterone stimulus Inferred from direct assay. Source: BHF-UCL salivary gland morphogenesis Inferred from expression pattern. Source: BHF-UCL somatic stem cell division Inferred from sequence or structural similarity. Source: UniProtKB transforming growth factor beta receptor signaling pathway Inferred from direct assay. Source: BHF-UCL
Cellular component	axon Inferred from sequence or structural similarity. Source: UniProtKB extracellular matrix Inferred from direct assay. Source: BHF-UCL extracellular space Inferred from electronic annotation. Source: InterPro neuronal cell body Inferred from sequence or structural similarity. Source: UniProtKB platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular function	beta-amyloid binding Inferred from direct assay. Source: UniProtKB cytokine activity Traceable author statement. Source: UniProtKB growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW protein heterodimerization activity Traceable author statement. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB receptor signaling protein serine/threonine kinase activity Inferred from direct assay. Source: BHF-UCL type II transforming growth factor beta receptor binding Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	6	EBI-779581,EBI-77613

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P61812-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: P61812-2)

The sequence of this isoform differs from the canonical sequence as follows:
     116-116: N → TVCPVVTTPSGSVGSLCSRQSQVLCGYLD

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Propeptide

20 – 302

283

PRO_0000033784

Chain

303 – 414

112

Transforming growth factor beta-2

PRO_0000033785

Amino acid modifications

Glycosylation

72

1

N-linked (GlcNAc...) Potential

Glycosylation

140

1

N-linked (GlcNAc...) Potential

Glycosylation

241

1

N-linked (GlcNAc...) Potential

Disulfide bond

309 ↔ 318

Disulfide bond

317 ↔ 380

Disulfide bond

346 ↔ 411

Disulfide bond

350 ↔ 413

Disulfide bond

379

Interchain

Natural variations

Alternative sequence

116

1

N → TVCPVVTTPSGSVGSLCSRQ SQVLCGYLD in isoform B.

VSP_006417

Natural variant

91

1

R → H. Ref.4 Ref.14
Corresponds to variant rs10482721 [ dbSNP | Ensembl ].

VAR_012708

Natural variant

207

1

V → L. Ref.4
Corresponds to variant rs10482810 [ dbSNP | Ensembl ].

VAR_018923

Experimental info

Sequence conflict

32

1

F → L in AAA61162. Ref.8

Secondary structure

1

.

.

.

.

.

.

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.

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.

.

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.

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.

.

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414

Helix Strand Turn

Details...

Helix

306 – 309

4

Beta strand

315 – 320

6

Beta strand

323 – 325

3

Helix

326 – 330

5

Beta strand

335 – 337

3

Beta strand

339 – 342

4

Beta strand

345 – 347

3

Beta strand

354 – 356

3

Helix

359 – 370

12

Helix

372 – 374

3

Beta strand

379 – 382

4

Beta strand

384 – 394

11

Beta strand

397 – 408

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified August 1, 1988. Version 1. Checksum: 7D9D569E0F4A07D0	FASTA	414	47,748
	10 20 30 40 50 60 MHYCVLSAFL ILHLVTVALS LSTCSTLDMD QFMRKRIEAI RGQILSKLKL TSPPEDYPEP 70 80 90 100 110 120 EEVPPEVISI YNSTRDLLQE KASRRAAACE RERSDEEYYA KEVYKIDMPP FFPSENAIPP 130 140 150 160 170 180 TFYRPYFRIV RFDVSAMEKN ASNLVKAEFR VFRLQNPKAR VPEQRIELYQ ILKSKDLTSP 190 200 210 220 230 240 TQRYIDSKVV KTRAEGEWLS FDVTDAVHEW LHHKDRNLGF KISLHCPCCT FVPSNNYIIP 250 260 270 280 290 300 NKSEELEARF AGIDGTSTYT SGDQKTIKST RKKNSGKTPH LLLMLLPSYR LESQQTNRRK 310 320 330 340 350 360 KRALDAAYCF RNVQDNCCLR PLYIDFKRDL GWKWIHEPKG YNANFCAGAC PYLWSSDTQH 370 380 390 400 410 SRVLSLYNTI NPEASASPCC VSQDLEPLTI LYYIGKTPKI EQLSNMIVKS CKCS
	Isoform B [UniParc] [UniParc]. Checksum: 5D7A3C2ED51753D5	FASTA	442	50,573
	10 20 30 40 50 60 MHYCVLSAFL ILHLVTVALS LSTCSTLDMD QFMRKRIEAI RGQILSKLKL TSPPEDYPEP 70 80 90 100 110 120 EEVPPEVISI YNSTRDLLQE KASRRAAACE RERSDEEYYA KEVYKIDMPP FFPSETVCPV 130 140 150 160 170 180 VTTPSGSVGS LCSRQSQVLC GYLDAIPPTF YRPYFRIVRF DVSAMEKNAS NLVKAEFRVF 190 200 210 220 230 240 RLQNPKARVP EQRIELYQIL KSKDLTSPTQ RYIDSKVVKT RAEGEWLSFD VTDAVHEWLH 250 260 270 280 290 300 HKDRNLGFKI SLHCPCCTFV PSNNYIIPNK SEELEARFAG IDGTSTYTSG DQKTIKSTRK 310 320 330 340 350 360 KNSGKTPHLL LMLLPSYRLE SQQTNRRKKR ALDAAYCFRN VQDNCCLRPL YIDFKRDLGW 370 380 390 400 410 420 KWIHEPKGYN ANFCAGACPY LWSSDTQHSR VLSLYNTINP EASASPCCVS QDLEPLTILY 430 440 YIGKTPKIEQ LSNMIVKSCK CS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family." de Martin R., Haendler B., Hofer-Warbinek R., Gaugitsch H., Wrann M., Schluesener H., Seifert J.M., Bodmer S., Fontana A., Hofer E. EMBO J. 6:3673-3677(1987) [PubMed: 3322813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]	"Transforming growth factor-beta 2: cDNA cloning and sequence analysis." Madisen L., Webb N.R., Rose T.M., Marquardt H., Ikeda T., Twardzik D.R., Seyedin S., Purchio A.F. DNA 7:1-8(1988) [PubMed: 3162414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
[3]	"Structural and sequence analysis of TGF-beta 2 cDNA clones predicts two different precursor proteins produced by alternative mRNA splicing." Webb N.R., Madisen L., Rose T.M., Purchio A.F. DNA 7:493-497(1988) [PubMed: 2850146] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
[4]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-91 AND LEU-207.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Tissue: Thalamus.
[6]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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].
[8]	"Molecular cloning and structure of the human transforming growth factor-beta 2 gene promoter." Noma T., Glick A.B., Geiser A.G., O'Reilly M.A., Miller J., Roberts A.B., Sporn M.B. Growth Factors 4:247-255(1991) [PubMed: 1764261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-115. Tissue: Lung.
[9]	"Complete amino acid sequence of human transforming growth factor type beta 2." Marquardt H., Lioubin M.N., Ikeda T. J. Biol. Chem. 262:12127-12131(1987) [PubMed: 3476488] [Abstract] Cited for: PROTEIN SEQUENCE OF 303-414.
[10]	"Molecular characterization of a familial translocation implicates disruption of HDAC9 and possible position effect on TGFbeta2 in the pathogenesis of Peters' anomaly." David D., Cardoso J., Marques B., Marques R., Silva E.D., Santos H., Boavida M.G. Genomics 81:489-503(2003) [PubMed: 12706107] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH HDAC9.
[11]	"Mechanisms for asporin function and regulation in articular cartilage." Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S. J. Biol. Chem. 282:32185-32192(2007) [PubMed: 17827158] [Abstract] Cited for: INTERACTION WITH ASPN.
[12]	"Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily." Daopin S., Piez K.A., Ogawa Y., Davies D.R. Science 257:369-373(1992) [PubMed: 1631557] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[13]	"An unusual feature revealed by the crystal structure at 2.2-A resolution of human transforming growth factor-beta 2." Schlunegger M.P., Gruetter M.G. Nature 358:430-434(1992) [PubMed: 1641027] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[14]	"Two novel polymorphisms in the human transforming growth factor beta 2 gene." Alansari A., Hajeer A.H., Bayat A., Eyre S., Carthy D., Ollier W.E. Genes Immun. 2:295-296(2001) [PubMed: 11528528] [Abstract] Cited for: VARIANT HIS-91.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

TGF beta-2 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00083 mRNA. Translation: CAA68279.1.
M19154 mRNA. Translation: AAA50404.1.
M19154 mRNA. Translation: AAA50405.1. Sequence problems.
AY438979 Genomic DNA. Translation: AAR05442.1.
AK296504 mRNA. Translation: BAG59137.1.
CH471100 Genomic DNA. Translation: EAW93326.1.
BC096235 mRNA. Translation: AAH96235.1.
BC099635 mRNA. Translation: AAH99635.1.
M87843 Genomic DNA. Translation: AAA61162.1.

IPI

IPI00220156.
IPI00235354.

PIR

B31249. A29478.
A31249. S06216.

RefSeq

NP_001129071.1. NM_001135599.2.
NP_003229.1. NM_003238.3.

UniGene

Hs.133379.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TFG	X-ray	1.95	A	303-414	[»]
2TGI	X-ray	1.80	A	303-414	[»]

ProteinModelPortal

P61812.

SMR

P61812. Positions 21-414.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5936N.

IntAct

P61812. 1 interaction.

STRING

P61812.

PTM databases

PhosphoSite

P61812.

Polymorphism databases

DMDM

48429157.

Proteomic databases

PRIDE

P61812.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366930; ENSP00000355897; ENSG00000092969.

GeneID

7042.

KEGG

hsa:7042.

UCSC

uc001hlm.1. human.
uc001hln.1. human.

Organism-specific databases

CTD

7042.

GeneCards

GC01P218519.

HGNC

HGNC:11768. TGFB2.

MIM

190220. gene.

neXtProt

NX_P61812.

Orphanet

708. Peters anomaly.

PharmGKB

PA36482.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19448.

GeneTree

ENSGT00560000076548.

HOVERGEN

HBG074115.

OMA

RAATCER.

OrthoDB

EOG43TZVH.

Enzyme and pathway databases

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.
hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P61812.

Bgee

P61812.

CleanEx

HS_TGFB2.

Genevestigator

P61812.

GermOnline

ENSG00000092969. Homo sapiens.

Family and domain databases

InterPro

IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR016319. TGF-beta.
IPR015615. TGF-beta-rel.
IPR003940. TGFb2.
IPR017948. TGFb_CS.
[Graphical view]

KO

K13376.

PANTHER

PTHR11848. TGFbeta. 1 hit.

Pfam

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

PIRSF

PIRSF001787. TGF-beta. 1 hit.

PRINTS

PR01423. TGFBETA.
PR01425. TGFBETA2.

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

NextBio

27517.

PMAP-CutDB

P61812.

SOURCE

Search...

Entry information

Entry name

TGFB2_HUMAN

Accession

Primary (citable) accession number: P61812
Secondary accession number(s): B4DKC5 , P08112, Q15579, Q15581, Q4VAV9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	August 1, 1988
Last modified:	January 25, 2012
This is version 99 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.