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Protein

Protransforming growth factor alpha

Gene

TGFA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • activation of MAPK activity Source: HGNC
  • cell proliferation Source: ProtInc
  • COPII vesicle coating Source: Reactome
  • ER to Golgi vesicle-mediated transport Source: Reactome
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of epidermal growth factor-activated receptor activity Source: HGNC
  • positive regulation of epithelial cell proliferation Source: HGNC
  • positive regulation of mitotic nuclear division Source: HGNC
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163235-MONOMER.
ReactomeiR-HSA-204005. COPII (Coat Protein 2) 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.
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

HGNCiHGNC:11765. TGFA.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • basolateral plasma membrane Source: BHF-UCL
  • cell surface Source: BHF-UCL
  • cytoplasmic vesicle Source: BHF-UCL
  • endoplasmic reticulum-Golgi intermediate compartment membrane Source: Reactome
  • endoplasmic reticulum membrane Source: Reactome
  • ER to Golgi transport vesicle membrane Source: Reactome
  • extracellular space Source: BHF-UCL
  • Golgi membrane Source: GOC
  • integral component of plasma membrane Source: GO_Central
  • perinuclear region of cytoplasm Source: BHF-UCL
  • plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi7039.
MalaCardsiTGFA.
OpenTargetsiENSG00000163235.
Orphaneti1991. Cleft lip with or without cleft palate.
2227. 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...)Sequence 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.

PTM databases

SwissPalmiP01135.

Miscellaneous databases

PMAP-CutDBP01135.

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.
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

WithEntry#Exp.IntActNotes
EGFRP005332EBI-1034374,EBI-297353
Magi3Q9EQJ94EBI-1034374,EBI-7455245From a different organism.
SGTAO437653EBI-1034374,EBI-347996

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112897. 9 interactors.
DIPiDIP-5765N.
IntActiP01135. 9 interactors.
MINTiMINT-121235.
STRINGi9606.ENSP00000295400.

Structurei

Secondary structure

1160
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi43 – 45Combined sources3
Helixi51 – 54Combined sources4
Beta strandi58 – 63Combined sources6
Turni64 – 67Combined sources4
Beta strandi68 – 73Combined sources6
Beta strandi77 – 79Combined sources3
Beta strandi84 – 86Combined sources3

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...

Miscellaneous databases

EvolutionaryTraceiP01135.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IVW5. Eukaryota.
ENOG4111Z4I. LUCA.
GeneTreeiENSGT00730000110951.
HOGENOMiHOG000013036.
HOVERGENiHBG000330.
InParanoidiP01135.
KOiK08774.
OMAiLIHCCEV.
PhylomeDBiP01135.
TreeFamiTF332938.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

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

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

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 rs11466259dbSNPEnsembl.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

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. 9 interactors.
DIPiDIP-5765N.
IntActiP01135. 9 interactors.
MINTiMINT-121235.
STRINGi9606.ENSP00000295400.

PTM databases

SwissPalmiP01135.

Polymorphism and mutation databases

BioMutaiTGFA.
DMDMi135689.

Proteomic databases

PaxDbiP01135.
PeptideAtlasiP01135.
PRIDEiP01135.

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.
GeneCardsiTGFA.
HGNCiHGNC:11765. TGFA.
HPAiHPA042297.
MalaCardsiTGFA.
MIMi190170. gene.
neXtProtiNX_P01135.
OpenTargetsiENSG00000163235.
Orphaneti1991. Cleft lip with or without cleft palate.
2227. Hypodontia.
99798. Oligodontia.
PharmGKBiPA36480.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVW5. Eukaryota.
ENOG4111Z4I. LUCA.
GeneTreeiENSGT00730000110951.
HOGENOMiHOG000013036.
HOVERGENiHBG000330.
InParanoidiP01135.
KOiK08774.
OMAiLIHCCEV.
PhylomeDBiP01135.
TreeFamiTF332938.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163235-MONOMER.
ReactomeiR-HSA-204005. COPII (Coat Protein 2) 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.
SignaLinkiP01135.
SIGNORiP01135.

Miscellaneous databases

ChiTaRSiTGFA. human.
EvolutionaryTraceiP01135.
GeneWikiiTGF_alpha.
GenomeRNAii7039.
PMAP-CutDBP01135.
PROiP01135.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163235.
CleanExiHS_TGFA.
ExpressionAtlasiP01135. baseline and differential.
GenevisibleiP01135. HS.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTGFA_HUMAN
AccessioniPrimary (citable) accession number: P01135
Secondary accession number(s): A8K286
, Q15577, Q53SK7, Q9BS56, Q9UEI3, Q9UKM1, Q9UKM2, Q9UKM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 182 of the entry and version 1 of the sequence. [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
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.