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Protein

Probetacellulin

Gene

BTC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members. Potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

Enzyme and pathway databases

ReactomeiR-HSA-1227986. Signaling by ERBB2.
R-HSA-1236394. Signaling by ERBB4.
R-HSA-1250196. SHC1 events in ERBB2 signaling.
R-HSA-1250342. PI3K events in ERBB4 signaling.
R-HSA-1250347. SHC1 events in ERBB4 signaling.
R-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1963640. GRB2 events in ERBB2 signaling.
R-HSA-1963642. PI3K events in ERBB2 signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6785631. ERBB2 Regulates Cell Motility.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8847993. ERBB2 Activates PTK6 Signaling.
SignaLinkiP35070.
SIGNORiP35070.

Names & Taxonomyi

Protein namesi
Recommended name:
Probetacellulin
Cleaved into the following chain:
Betacellulin
Short name:
BTC
Gene namesi
Name:BTC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:1121. BTC.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini32 – 11887ExtracellularSequence analysisAdd
BLAST
Transmembranei119 – 13921HelicalSequence analysisAdd
BLAST
Topological domaini140 – 17839CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA25442.

Polymorphism and mutation databases

BioMutaiBTC.
DMDMi461653.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131By similarityAdd
BLAST
Chaini32 – 178147ProbetacellulinPRO_0000300685Add
BLAST
Chaini32 – 11180BetacellulinPRO_0000007490Add
BLAST
Propeptidei112 – 17867Removed in mature formBy similarityPRO_0000007491Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi34 – 341N-linked (GlcNAc...)Sequence analysis
Disulfide bondi69 ↔ 82
Disulfide bondi77 ↔ 93
Disulfide bondi95 ↔ 104

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP35070.
PRIDEiP35070.

PTM databases

SwissPalmiP35070.

Expressioni

Tissue specificityi

Synthesized in several tissues and tumor cells. Predominantly expressed in pancreas and small intestine.1 Publication

Gene expression databases

BgeeiP35070.
CleanExiHS_BTC.
ExpressionAtlasiP35070. baseline and differential.
GenevisibleiP35070. HS.

Interactioni

Subunit structurei

Monomer. Interacts with EGFR and ERBB4.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GMPPAQ96IJ63EBI-6590057,EBI-750953
KRT31Q153233EBI-6590057,EBI-948001
S100A4P264472EBI-6590057,EBI-717058

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: ProtInc
  • growth factor activity Source: ProtInc

Protein-protein interaction databases

BioGridi107150. 3 interactions.
DIPiDIP-5768N.
IntActiP35070. 4 interactions.
MINTiMINT-7256522.
STRINGi9606.ENSP00000379092.

Structurei

Secondary structure

1
178
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi66 – 683Combined sources
Helixi71 – 733Combined sources
Beta strandi82 – 854Combined sources
Turni86 – 894Combined sources
Beta strandi90 – 934Combined sources
Turni101 – 1044Combined sources
Beta strandi106 – 1083Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IOXNMR-A62-111[»]
1IP0NMR-A62-111[»]
ProteinModelPortaliP35070.
SMRiP35070. Positions 62-111.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35070.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini65 – 10541EGF-likePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi146 – 1549Arg/Lys-rich (basic)

Sequence similaritiesi

Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWUI. Eukaryota.
ENOG41126JP. LUCA.
GeneTreeiENSGT00730000110951.
HOGENOMiHOG000237352.
HOVERGENiHBG004905.
InParanoidiP35070.
KOiK09783.
OMAiIGARCER.
PhylomeDBiP35070.
TreeFamiTF332938.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF12661. hEGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P35070-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDRAARCSGA SSLPLLLALA LGLVILHCVV ADGNSTRSPE TNGLLCGDPE
60 70 80 90 100
ENCAATTTQS KRKGHFSRCP KQYKHYCIKG RCRFVVAEQT PSCVCDEGYI
110 120 130 140 150
GARCERVDLF YLRGDRGQIL VICLIAVMVV FIILVIGVCT CCHPLRKRRK
160 170
RKKKEEEMET LGKDITPINE DIEETNIA
Length:178
Mass (Da):19,746
Last modified:February 1, 1994 - v1
Checksum:i27AC77BD92001F0F
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71C → G.
Corresponds to variant rs28549760 [ dbSNP | Ensembl ].
VAR_029307
Natural varianti44 – 441L → F.
Corresponds to variant rs56320257 [ dbSNP | Ensembl ].
VAR_061151
Natural varianti124 – 1241L → M.1 Publication
Corresponds to variant rs11938093 [ dbSNP | Ensembl ].
VAR_029308

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S55606 mRNA. Translation: AAB25452.1.
BC011618 mRNA. Translation: AAH11618.1.
CCDSiCCDS3566.1.
PIRiJC1467.
RefSeqiNP_001303892.1. NM_001316963.1.
NP_001720.1. NM_001729.3.
XP_011530513.1. XM_011532211.1.
UniGeneiHs.591704.
Hs.710156.

Genome annotation databases

EnsembliENST00000395743; ENSP00000379092; ENSG00000174808.
GeneIDi685.
KEGGihsa:685.
UCSCiuc003hig.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S55606 mRNA. Translation: AAB25452.1.
BC011618 mRNA. Translation: AAH11618.1.
CCDSiCCDS3566.1.
PIRiJC1467.
RefSeqiNP_001303892.1. NM_001316963.1.
NP_001720.1. NM_001729.3.
XP_011530513.1. XM_011532211.1.
UniGeneiHs.591704.
Hs.710156.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IOXNMR-A62-111[»]
1IP0NMR-A62-111[»]
ProteinModelPortaliP35070.
SMRiP35070. Positions 62-111.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107150. 3 interactions.
DIPiDIP-5768N.
IntActiP35070. 4 interactions.
MINTiMINT-7256522.
STRINGi9606.ENSP00000379092.

PTM databases

SwissPalmiP35070.

Polymorphism and mutation databases

BioMutaiBTC.
DMDMi461653.

Proteomic databases

PaxDbiP35070.
PRIDEiP35070.

Protocols and materials databases

DNASUi685.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395743; ENSP00000379092; ENSG00000174808.
GeneIDi685.
KEGGihsa:685.
UCSCiuc003hig.3. human.

Organism-specific databases

CTDi685.
GeneCardsiBTC.
HGNCiHGNC:1121. BTC.
MIMi600345. gene.
neXtProtiNX_P35070.
PharmGKBiPA25442.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWUI. Eukaryota.
ENOG41126JP. LUCA.
GeneTreeiENSGT00730000110951.
HOGENOMiHOG000237352.
HOVERGENiHBG004905.
InParanoidiP35070.
KOiK09783.
OMAiIGARCER.
PhylomeDBiP35070.
TreeFamiTF332938.

Enzyme and pathway databases

ReactomeiR-HSA-1227986. Signaling by ERBB2.
R-HSA-1236394. Signaling by ERBB4.
R-HSA-1250196. SHC1 events in ERBB2 signaling.
R-HSA-1250342. PI3K events in ERBB4 signaling.
R-HSA-1250347. SHC1 events in ERBB4 signaling.
R-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1963640. GRB2 events in ERBB2 signaling.
R-HSA-1963642. PI3K events in ERBB2 signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6785631. ERBB2 Regulates Cell Motility.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8847993. ERBB2 Activates PTK6 Signaling.
SignaLinkiP35070.
SIGNORiP35070.

Miscellaneous databases

ChiTaRSiBTC. human.
EvolutionaryTraceiP35070.
GenomeRNAii685.
PROiP35070.
SOURCEiSearch...

Gene expression databases

BgeeiP35070.
CleanExiHS_BTC.
ExpressionAtlasiP35070. baseline and differential.
GenevisibleiP35070. HS.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF12661. hEGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of cDNA encoding human betacellulin, a new member of the EGF family."
    Sasada R., Ono Y., Taniyama Y., Shing Y., Folkman J., Igarashi K.
    Biochem. Biophys. Res. Commun. 190:1173-1179(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Mammary gland.
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-124.
    Tissue: Ovary.
  3. "Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction."
    Watanabe T., Shintani A., Nakata M., Shing Y., Folkman J., Igarashi K., Sasada R.
    J. Biol. Chem. 269:9966-9973(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION AS EGFR LIGAND.
  4. "Human betacellulin, a member of the EGF family dominantly expressed in pancreas and small intestine, is fully active in a monomeric form."
    Seno M., Tada H., Kosaka M., Sasada R., Igarashi K., Shing Y., Folkman J., Ueda M., Yamada H.
    Growth Factors 13:181-191(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta."
    Riese D.J. II, Bermingham Y., van Raaij T.M., Buckley S., Plowman G.D., Stern D.F.
    Oncogene 12:345-353(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH EGFR AND ERBB4.
  6. "Ligand discrimination in signaling through an ErbB4 receptor homodimer."
    Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C., Carraway K.L. III
    J. Biol. Chem. 275:19803-19807(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ERBB4.
  7. "Solution structure of betacellulin, a new member of EGF-family ligands."
    Miura K., Doura H., Aizawa T., Tada H., Seno M., Yamada H., Kawano K.
    Biochem. Biophys. Res. Commun. 294:1040-1046(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 62-111.

Entry informationi

Entry nameiBTC_HUMAN
AccessioniPrimary (citable) accession number: P35070
Secondary accession number(s): Q96F48
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: June 8, 2016
This is version 147 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 4
    Human chromosome 4: 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.