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Protein

Protransforming growth factor alpha

Gene

TGFA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar.

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: UniProtKB
  • growth factor activity Source: HGNC

GO - Biological processi

Keywordsi

Molecular functionGrowth factor, Mitogen

Enzyme and pathway databases

ReactomeiR-HSA-204005 COPII-mediated vesicle transport
R-HSA-5694530 Cargo concentration in the ER
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiP01135
SIGNORiP01135

Names & Taxonomyi

Protein namesi
Recommended name:
Protransforming growth factor alpha
Cleaved into the following chain:
Alternative name(s):
EGF-like TGF
Short name:
ETGF
TGF type 1
Gene namesi
Name:TGFA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000163235.15
HGNCiHGNC:11765 TGFA
MIMi190170 gene
neXtProtiNX_P01135

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 98ExtracellularSequence analysisAdd BLAST75
Transmembranei99 – 124HelicalSequence analysisAdd BLAST26
Topological domaini125 – 160CytoplasmicSequence analysisAdd BLAST36

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi7039
MalaCardsiTGFA
OpenTargetsiENSG00000163235
Orphaneti2227 NON RARE IN EUROPE: Hypodontia
99798 Oligodontia
PharmGKBiPA36480

Polymorphism and mutation databases

BioMutaiTGFA
DMDMi135689

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000030274424 – 160Protransforming growth factor alphaAdd BLAST137
PropeptideiPRO_000000775224 – 39Removed in mature formAdd BLAST16
ChainiPRO_000000775340 – 89Transforming growth factor alphaAdd BLAST50
PropeptideiPRO_000000775490 – 160Removed in mature formAdd BLAST71

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi25N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi47 ↔ 60PROSITE-ProRule annotation1 Publication
Disulfide bondi55 ↔ 71PROSITE-ProRule annotation1 Publication
Disulfide bondi73 ↔ 82PROSITE-ProRule annotation1 Publication
Lipidationi153S-palmitoyl cysteine1 Publication1
Lipidationi154S-palmitoyl cysteine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP01135
PeptideAtlasiP01135
PRIDEiP01135
ProteomicsDBi51332
51333 [P01135-2]
51334 [P01135-3]
51335 [P01135-4]
51336 [P01135-5]

PTM databases

SwissPalmiP01135

Miscellaneous databases

PMAP-CutDBiP01135

Expressioni

Tissue specificityi

Isoform 1, isoform 3 and isoform 4 are expressed in keratinocytes and tumor-derived cell lines.1 Publication

Gene expression databases

BgeeiENSG00000163235 Expressed in 192 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_TGFA
ExpressionAtlasiP01135 baseline and differential
GenevisibleiP01135 HS

Organism-specific databases

HPAiHPA042297

Interactioni

Subunit structurei

Interacts with the PDZ domains of MAGI3, SDCBP and SNTA1. The interaction with SDCBP, is required for the targeting to the cell surface. In the endoplasmic reticulum, in its immature form (i.e. with a prosegment and lacking full N-glycosylation), interacts with CNIH. In the Golgi apparatus, may form a complex with CNIH and GORASP2. Interacts (via cytoplasmic C-terminal domain) with NKD2.3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112897, 68 interactors
DIPiDIP-5765N
IntActiP01135, 10 interactors
MINTiP01135
STRINGi9606.ENSP00000295400

Structurei

Secondary structure

1160
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP01135
SMRiP01135
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01135

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 83EGF-likePROSITE-ProRule annotationAdd BLAST41

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IVW5 Eukaryota
ENOG4111Z4I LUCA
GeneTreeiENSGT00730000110951
HOGENOMiHOG000013036
HOVERGENiHBG000330
InParanoidiP01135
KOiK08774
OMAiCQALICR
PhylomeDBiP01135
TreeFamiTF332938

Family and domain databases

InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR015497 EGF_rcpt_ligand
PANTHERiPTHR10740 PTHR10740, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 1 hit
PS50026 EGF_3, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P01135-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MVPSAGQLAL FALGIVLAAC QALENSTSPL SADPPVAAAV VSHFNDCPDS
60 70 80 90 100
HTQFCFHGTC RFLVQEDKPA CVCHSGYVGA RCEHADLLAV VAASQKKQAI
110 120 130 140 150
TALVVVSIVA LAVLIITCVL IHCCQVRKHC EWCRALICRH EKPSALLKGR
160
TACCHSETVV
Length:160
Mass (Da):17,006
Last modified:July 21, 1986 - v1
Checksum:iD692184F9353DE47
GO
Isoform 2 (identifier: P01135-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     32-32: Missing.

Show »
Length:159
Mass (Da):16,935
Checksum:i41949AAD26D0BF65
GO
Isoform 3 (identifier: P01135-3) [UniParc]FASTAAdd to basket
Also known as: VaII

The sequence of this isoform differs from the canonical sequence as follows:
     32-32: Missing.
     159-160: VV → ATLG

Show »
Length:161
Mass (Da):17,079
Checksum:i94BA72EB8AAD26D0
GO
Isoform 4 (identifier: P01135-4) [UniParc]FASTAAdd to basket
Also known as: VaI

The sequence of this isoform differs from the canonical sequence as follows:
     159-160: VV → GCRLY

Show »
Length:163
Mass (Da):17,400
Checksum:i0E207CBAF8A84F93
GO
Isoform 5 (identifier: P01135-5) [UniParc]FASTAAdd to basket
Also known as: VaIM

The sequence of this isoform differs from the canonical sequence as follows:
     32-32: Missing.
     159-160: VV → GCRLY

Show »
Length:162
Mass (Da):17,329
Checksum:iD4ABF94DFE2AAD26
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VNR3F8VNR3_HUMAN
Protransforming growth factor alpha
TGFA
166Annotation score:
E7EPT6E7EPT6_HUMAN
Protransforming growth factor alpha
TGFA
165Annotation score:
F8WA74F8WA74_HUMAN
Protransforming growth factor alpha
TGFA
120Annotation score:
H0Y6S5H0Y6S5_HUMAN
Protransforming growth factor alpha
TGFA
131Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti58G → A in AAA61157 (PubMed:2464748).Curated1
Sequence conflicti65Q → H in AAA61157 (PubMed:2464748).Curated1
Sequence conflicti159V → L in AAA61157 (PubMed:2464748).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024271109V → M. Corresponds to variant dbSNP:rs11466259Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03836932Missing in isoform 2, isoform 3 and isoform 5. 3 Publications1
Alternative sequenceiVSP_038370159 – 160VV → ATLG in isoform 3. 1 Publication2
Alternative sequenceiVSP_038371159 – 160VV → GCRLY in isoform 4 and isoform 5. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03222 mRNA Translation: AAA61159.1
M31172 mRNA Translation: AAA61157.1
X70340 mRNA Translation: CAA49806.1
AF123243
, AF123238, AF123239, AF123240, AF123241, AF123242 Genomic DNA Translation: AAF13491.1
AY325886
, AY325885, AY326405, AY327131, AY327132, AY329368 Genomic DNA Translation: AAP97822.2
AF149096 mRNA Translation: AAF05089.1
AF149097 mRNA Translation: AAF05090.1
AF149098 mRNA Translation: AAF05091.1
BT006833 mRNA Translation: AAP35479.1
AK290151 mRNA Translation: BAF82840.1
AC005234 Genomic DNA Translation: AAY14793.1
AC017084 Genomic DNA Translation: AAY14705.1
CH471053 Genomic DNA Translation: EAW99810.1
CH471053 Genomic DNA Translation: EAW99812.1
BC005308 mRNA Translation: AAH05308.1
M22440 Genomic DNA Translation: AAA52530.1
AF075584, AF075583 Genomic DNA Translation: AAD12238.1
CCDSiCCDS1905.1 [P01135-1]
CCDS46316.1 [P01135-2]
PIRiJN0876 WFHU1
RefSeqiNP_001093161.1, NM_001099691.2 [P01135-2]
NP_001295087.1, NM_001308158.1
NP_001295088.1, NM_001308159.1
NP_003227.1, NM_003236.3 [P01135-1]
UniGeneiHs.170009
Hs.628298

Genome annotation databases

EnsembliENST00000295400; ENSP00000295400; ENSG00000163235 [P01135-1]
ENST00000418333; ENSP00000404099; ENSG00000163235 [P01135-2]
ENST00000445399; ENSP00000387493; ENSG00000163235 [P01135-3]
GeneIDi7039
KEGGihsa:7039
UCSCiuc002sgs.4 human [P01135-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03222 mRNA Translation: AAA61159.1
M31172 mRNA Translation: AAA61157.1
X70340 mRNA Translation: CAA49806.1
AF123243
, AF123238, AF123239, AF123240, AF123241, AF123242 Genomic DNA Translation: AAF13491.1
AY325886
, AY325885, AY326405, AY327131, AY327132, AY329368 Genomic DNA Translation: AAP97822.2
AF149096 mRNA Translation: AAF05089.1
AF149097 mRNA Translation: AAF05090.1
AF149098 mRNA Translation: AAF05091.1
BT006833 mRNA Translation: AAP35479.1
AK290151 mRNA Translation: BAF82840.1
AC005234 Genomic DNA Translation: AAY14793.1
AC017084 Genomic DNA Translation: AAY14705.1
CH471053 Genomic DNA Translation: EAW99810.1
CH471053 Genomic DNA Translation: EAW99812.1
BC005308 mRNA Translation: AAH05308.1
M22440 Genomic DNA Translation: AAA52530.1
AF075584, AF075583 Genomic DNA Translation: AAD12238.1
CCDSiCCDS1905.1 [P01135-1]
CCDS46316.1 [P01135-2]
PIRiJN0876 WFHU1
RefSeqiNP_001093161.1, NM_001099691.2 [P01135-2]
NP_001295087.1, NM_001308158.1
NP_001295088.1, NM_001308159.1
NP_003227.1, NM_003236.3 [P01135-1]
UniGeneiHs.170009
Hs.628298

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GK5NMR-A83-89[»]
1MOXX-ray2.50C/D40-89[»]
1YUFNMR-A40-89[»]
1YUGNMR-A40-89[»]
2TGFNMR-A40-89[»]
3E50X-ray2.30C/D40-89[»]
3TGFNMR-A40-89[»]
4TGFNMR-A40-89[»]
5KN5X-ray2.80C/F49-88[»]
ProteinModelPortaliP01135
SMRiP01135
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112897, 68 interactors
DIPiDIP-5765N
IntActiP01135, 10 interactors
MINTiP01135
STRINGi9606.ENSP00000295400

PTM databases

SwissPalmiP01135

Polymorphism and mutation databases

BioMutaiTGFA
DMDMi135689

Proteomic databases

PaxDbiP01135
PeptideAtlasiP01135
PRIDEiP01135
ProteomicsDBi51332
51333 [P01135-2]
51334 [P01135-3]
51335 [P01135-4]
51336 [P01135-5]

Protocols and materials databases

DNASUi7039
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295400; ENSP00000295400; ENSG00000163235 [P01135-1]
ENST00000418333; ENSP00000404099; ENSG00000163235 [P01135-2]
ENST00000445399; ENSP00000387493; ENSG00000163235 [P01135-3]
GeneIDi7039
KEGGihsa:7039
UCSCiuc002sgs.4 human [P01135-1]

Organism-specific databases

CTDi7039
DisGeNETi7039
EuPathDBiHostDB:ENSG00000163235.15
GeneCardsiTGFA
HGNCiHGNC:11765 TGFA
HPAiHPA042297
MalaCardsiTGFA
MIMi190170 gene
neXtProtiNX_P01135
OpenTargetsiENSG00000163235
Orphaneti2227 NON RARE IN EUROPE: Hypodontia
99798 Oligodontia
PharmGKBiPA36480
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVW5 Eukaryota
ENOG4111Z4I LUCA
GeneTreeiENSGT00730000110951
HOGENOMiHOG000013036
HOVERGENiHBG000330
InParanoidiP01135
KOiK08774
OMAiCQALICR
PhylomeDBiP01135
TreeFamiTF332938

Enzyme and pathway databases

ReactomeiR-HSA-204005 COPII-mediated vesicle transport
R-HSA-5694530 Cargo concentration in the ER
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiP01135
SIGNORiP01135

Miscellaneous databases

ChiTaRSiTGFA human
EvolutionaryTraceiP01135
GeneWikiiTGF_alpha
GenomeRNAii7039
PMAP-CutDBiP01135
PROiPR:P01135
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163235 Expressed in 192 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_TGFA
ExpressionAtlasiP01135 baseline and differential
GenevisibleiP01135 HS

Family and domain databases

InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR015497 EGF_rcpt_ligand
PANTHERiPTHR10740 PTHR10740, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 1 hit
PS50026 EGF_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTGFA_HUMAN
AccessioniPrimary (citable) accession number: P01135
Secondary accession number(s): A8K286
, Q15577, Q53SK7, Q9BS56, Q9UEI3, Q9UKM1, Q9UKM2, Q9UKM3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 7, 2018
This is version 195 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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