P35070 (BTC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probetacellulin

Cleaved into the following chain:

1. Betacellulin
   Short name=BTC

Gene names

Name:

BTC

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	178 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	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. Ref.5
Subunit structure	Monomer. Interacts with EGFR and ERBB4. Ref.5 Ref.6
Subcellular location	Betacellulin: Secreted › extracellular space. Probetacellulin: Cell membrane; Single-pass type I membrane protein.
Tissue specificity	Synthesized in several tissues and tumor cells. Predominantly expressed in pancreas and small intestine. Ref.4
Sequence similarities	Contains 1 EGF-like domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Molecular function	Growth factor Mitogen
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Traceable author statement. Source: ProtInc
Molecular function	epidermal growth factor receptor binding Traceable author statement. Source: ProtInc growth factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

By similarity

Chain

32 – 178

147

Probetacellulin

PRO_0000300685

Chain

32 – 111

80

Betacellulin

PRO_0000007490

Propeptide

112 – 178

67

Removed in mature form By similarity

PRO_0000007491

Regions

Topological domain

32 – 118

87

Extracellular Potential

Transmembrane

119 – 139

21

Helical; Potential

Topological domain

140 – 178

39

Cytoplasmic Potential

Domain

65 – 105

41

EGF-like

Compositional bias

146 – 154

9

Arg/Lys-rich (basic)

Amino acid modifications

Glycosylation

34

1

N-linked (GlcNAc...) Potential

Disulfide bond

69 ↔ 82

Disulfide bond

77 ↔ 93

Disulfide bond

95 ↔ 104

Natural variations

Natural variant

7

1

C → G.
Corresponds to variant rs28549760 [ dbSNP | Ensembl ].

VAR_029307

Natural variant

44

1

L → F.
Corresponds to variant rs56320257 [ dbSNP | Ensembl ].

VAR_061151

Natural variant

124

1

L → M. Ref.2
Corresponds to variant rs11938093 [ dbSNP | Ensembl ].

VAR_029308

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

178

Helix Strand Turn

Details...

Beta strand

66 – 68

3

Helix

71 – 73

3

Beta strand

78 – 85

8

Turn

86 – 89

4

Beta strand

90 – 95

6

Turn

101 – 104

4

Beta strand

106 – 108

3

Sequences

	Sequence		Length	Mass (Da)
	P35070 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 27AC77BD92001F0F	FASTA	178	19,746
	10 20 30 40 50 60 MDRAARCSGA SSLPLLLALA LGLVILHCVV ADGNSTRSPE TNGLLCGDPE ENCAATTTQS 70 80 90 100 110 120 KRKGHFSRCP KQYKHYCIKG RCRFVVAEQT PSCVCDEGYI GARCERVDLF YLRGDRGQIL 130 140 150 160 170 VICLIAVMVV FIILVIGVCT CCHPLRKRRK RKKKEEEMET LGKDITPINE DIEETNIA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 8439318] [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: 15489334] [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: 8144591] [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: 8919026] [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: 8570211] [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: 10867024] [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: 12074582] [Abstract] Cited for: STRUCTURE BY NMR OF 62-111.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S55606 mRNA. Translation: AAB25452.1.
BC011618 mRNA. Translation: AAH11618.1.

IPI

IPI00015755.

PIR

JC1467.

RefSeq

NP_001720.1. NM_001729.2.

UniGene

Hs.710156.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IOX	NMR	-	A	62-111	[»]
1IP0	NMR	-	A	62-111	[»]

ProteinModelPortal

P35070.

SMR

P35070. Positions 62-111.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5768N.

MINT

MINT-7256522.

STRING

P35070.

Polymorphism databases

DMDM

461653.

Proteomic databases

PRIDE

P35070.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000311727; ENSP00000312050; ENSG00000174808.
ENST00000395743; ENSP00000379092; ENSG00000174808.

GeneID

685.

KEGG

hsa:685.

UCSC

uc003hig.2. human.

Organism-specific databases

CTD

685.

GeneCards

GC04M075669.

H-InvDB

HIX0004291.

HGNC

HGNC:1121. BTC.

MIM

600345. gene.

neXtProt

NX_P35070.

PharmGKB

PA25442.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08194.

HOGENOM

HBG126588.

HOVERGEN

HBG004905.

InParanoid

P35070.

OMA

CAATTTQ.

OrthoDB

EOG4WH8N4.

PhylomeDB

P35070.

Gene expression databases

ArrayExpress

P35070.

Bgee

P35070.

CleanEx

HS_BTC.

Genevestigator

P35070.

GermOnline

ENSG00000174808. Homo sapiens.

Family and domain databases

InterPro

IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR015497. EGF_rcpt_ligand.
[Graphical view]

KO

K09783.

PANTHER

PTHR10740. EGF_rcpt_ligand. 1 hit.

SMART

SM00181. EGF. 1 hit.
[Graphical view]

PROSITE

PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

2820.

SOURCE

Search...

Entry information

Entry name

BTC_HUMAN

Accession

Primary (citable) accession number: P35070
Secondary accession number(s): Q96F48

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	January 25, 2012
This is version 105 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.