EGF-containing fibulin-like extracellular matrix protein 1 precursor

Names and origin

Protein names

Recommended name:
    EGF-containing fibulin-like extracellular matrix protein 1
Alternative name(s):
    Fibulin-3
      Short name=FIBL-3
    Fibrillin-like protein
    Extracellular protein S1-5

Gene names

Name:	EFEMP1
Synonyms:	FBLN3, FBNL

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	493 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Subcellular location

Secreted.

Involvement in disease

Defects in EFEMP1 are a cause of Doyne honeycomb retinal dystrophy (DHRD) [MIM:126600]; also known as malattia leventinese (MLVT OR ML). DHRD is an autosomal dominant disease characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium. Ref.6 Ref.7

Sequence similarities

Belongs to the fibulin family.

Contains 6 EGF-like domains.

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Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	visual perception Ref.6 Traceable author statement. Source: ProtInc
Cellular component	proteinaceous extracellular matrix Ref.6 Traceable author statement. Source: ProtInc
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	3	EBI-536772,EBI-365961

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Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q12805-1) 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 2 (identifier: Q12805-2) The sequence of this isoform differs from the canonical sequence as follows: 1-8: Missing.

Isoform 3 (identifier: Q12805-3) The sequence of this isoform differs from the canonical sequence as follows: 58-58: Missing.

Isoform 4 (identifier: Q12805-4) The sequence of this isoform differs from the canonical sequence as follows: 106-106: Missing.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Chain

18 – 493

476

EGF-containing fibulin-like extracellular matrix protein 1

PRO_0000007570

Regions

Domain

26 – 71

46

EGF-like 1; atypical

Domain

173 – 213

41

EGF-like 2; calcium-binding Potential

Domain

214 – 253

40

EGF-like 3; calcium-binding Potential

Domain

254 – 293

40

EGF-like 4; calcium-binding Potential

Domain

294 – 333

40

EGF-like 5; calcium-binding Potential

Domain

334 – 378

45

EGF-like 6; calcium-binding Potential

Amino acid modifications

Glycosylation

249

1

N-linked (GlcNAc...) Potential

Disulfide bond

177 ↔ 190

By similarity

Disulfide bond

184 ↔ 199

By similarity

Disulfide bond

201 ↔ 212

By similarity

Disulfide bond

218 ↔ 228

By similarity

Disulfide bond

224 ↔ 237

By similarity

Disulfide bond

239 ↔ 252

By similarity

Disulfide bond

258 ↔ 268

By similarity

Disulfide bond

264 ↔ 277

By similarity

Disulfide bond

279 ↔ 292

By similarity

Disulfide bond

298 ↔ 309

By similarity

Disulfide bond

305 ↔ 318

By similarity

Disulfide bond

320 ↔ 332

By similarity

Disulfide bond

338 ↔ 350

By similarity

Disulfide bond

344 ↔ 359

By similarity

Disulfide bond

365 ↔ 377

By similarity

Natural variations

Alternative sequence

1 – 8

8

Missing in isoform 2.

VSP_001392

Alternative sequence

58

1

Missing in isoform 3.

VSP_001393

Alternative sequence

106

1

Missing in isoform 4.

VSP_001394

Natural variant

220

1

I → F Ref.6

VAR_009512

Natural variant

345

1

R → W in DHRD. Ref.6 Ref.7

VAR_009513

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 128CA5ED140DF414 Show »	FASTA	493	54,641
10 20 30 40 50 60 MLKALFLTML TLALVKSQDT EETITYTQCT DGYEWDPVRQ QCKDIDECDI VPDACKGGMK 70 80 90 100 110 120 CVNHYGGYLC LPKTAQIIVN NEQPQQETQP AEGTSGATTG VVAASSMATS GVLPGGGFVA 130 140 150 160 170 180 SAAAVAGPEM QTGRNNFVIR RNPADPQRIP SNPSHRIQCA AGYEQSEHNV CQDIDECTAG 190 200 210 220 230 240 THNCRADQVC INLRGSFACQ CPPGYQKRGE QCVDIDECTI PPYCHQRCVN TPGSFYCQCS 250 260 270 280 290 300 PGFQLAANNY TCVDINECDA SNQCAQQCYN ILGSFICQCN QGYELSSDRL NCEDIDECRT 310 320 330 340 350 360 SSYLCQYQCV NEPGKFSCMC PQGYQVVRSR TCQDINECET TNECREDEMC WNYHGGFRCY 370 380 390 400 410 420 PRNPCQDPYI LTPENRCVCP VSNAMCRELP QSIVYKYMSI RSDRSVPSDI FQIQATTIYA 430 440 450 460 470 480 NTINTFRIKS GNENGEFYLR QTSPVSAMLV LVKSLSGPRE HIVDLEMLTV SSIGTFRTSS 490 VLRLTIIVGP FSF « Hide
Isoform 2. Checksum: CF3DF7CCD89C58AC Show »	FASTA	485	53,722
10 20 30 40 50 60 MLTLALVKSQ DTEETITYTQ CTDGYEWDPV RQQCKDIDEC DIVPDACKGG MKCVNHYGGY 70 80 90 100 110 120 LCLPKTAQII VNNEQPQQET QPAEGTSGAT TGVVAASSMA TSGVLPGGGF VASAAAVAGP 130 140 150 160 170 180 EMQTGRNNFV IRRNPADPQR IPSNPSHRIQ CAAGYEQSEH NVCQDIDECT AGTHNCRADQ 190 200 210 220 230 240 VCINLRGSFA CQCPPGYQKR GEQCVDIDEC TIPPYCHQRC VNTPGSFYCQ CSPGFQLAAN 250 260 270 280 290 300 NYTCVDINEC DASNQCAQQC YNILGSFICQ CNQGYELSSD RLNCEDIDEC RTSSYLCQYQ 310 320 330 340 350 360 CVNEPGKFSC MCPQGYQVVR SRTCQDINEC ETTNECREDE MCWNYHGGFR CYPRNPCQDP 370 380 390 400 410 420 YILTPENRCV CPVSNAMCRE LPQSIVYKYM SIRSDRSVPS DIFQIQATTI YANTINTFRI 430 440 450 460 470 480 KSGNENGEFY LRQTSPVSAM LVLVKSLSGP REHIVDLEML TVSSIGTFRT SSVLRLTIIV GPFSF « Hide
Isoform 3. Checksum: FD09CF260582EA63 Show »	FASTA	492	54,583
10 20 30 40 50 60 MLKALFLTML TLALVKSQDT EETITYTQCT DGYEWDPVRQ QCKDIDECDI VPDACKGMKC 70 80 90 100 110 120 VNHYGGYLCL PKTAQIIVNN EQPQQETQPA EGTSGATTGV VAASSMATSG VLPGGGFVAS 130 140 150 160 170 180 AAAVAGPEMQ TGRNNFVIRR NPADPQRIPS NPSHRIQCAA GYEQSEHNVC QDIDECTAGT 190 200 210 220 230 240 HNCRADQVCI NLRGSFACQC PPGYQKRGEQ CVDIDECTIP PYCHQRCVNT PGSFYCQCSP 250 260 270 280 290 300 GFQLAANNYT CVDINECDAS NQCAQQCYNI LGSFICQCNQ GYELSSDRLN CEDIDECRTS 310 320 330 340 350 360 SYLCQYQCVN EPGKFSCMCP QGYQVVRSRT CQDINECETT NECREDEMCW NYHGGFRCYP 370 380 390 400 410 420 RNPCQDPYIL TPENRCVCPV SNAMCRELPQ SIVYKYMSIR SDRSVPSDIF QIQATTIYAN 430 440 450 460 470 480 TINTFRIKSG NENGEFYLRQ TSPVSAMLVL VKSLSGPREH IVDLEMLTVS SIGTFRTSSV 490 LRLTIIVGPF SF « Hide
Isoform 4. Checksum: EF7B59437CAA3C67 Show »	FASTA	492	54,553
10 20 30 40 50 60 MLKALFLTML TLALVKSQDT EETITYTQCT DGYEWDPVRQ QCKDIDECDI VPDACKGGMK 70 80 90 100 110 120 CVNHYGGYLC LPKTAQIIVN NEQPQQETQP AEGTSGATTG VVAASMATSG VLPGGGFVAS 130 140 150 160 170 180 AAAVAGPEMQ TGRNNFVIRR NPADPQRIPS NPSHRIQCAA GYEQSEHNVC QDIDECTAGT 190 200 210 220 230 240 HNCRADQVCI NLRGSFACQC PPGYQKRGEQ CVDIDECTIP PYCHQRCVNT PGSFYCQCSP 250 260 270 280 290 300 GFQLAANNYT CVDINECDAS NQCAQQCYNI LGSFICQCNQ GYELSSDRLN CEDIDECRTS 310 320 330 340 350 360 SYLCQYQCVN EPGKFSCMCP QGYQVVRSRT CQDINECETT NECREDEMCW NYHGGFRCYP 370 380 390 400 410 420 RNPCQDPYIL TPENRCVCPV SNAMCRELPQ SIVYKYMSIR SDRSVPSDIF QIQATTIYAN 430 440 450 460 470 480 TINTFRIKSG NENGEFYLRQ TSPVSAMLVL VKSLSGPREH IVDLEMLTVS SIGTFRTSSV 490 LRLTIIVGPF SF « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor-like repeat family stimulates DNA synthesis." Lecka-Czernik B., Lumpkin C.K. Jr., Goldstein S. Mol. Cell. Biol. 15:120-128(1995) [PubMed: 7799918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE ALTERNATIVE SPLICING. Tissue: Skin.
[2]	"Structure and chromosomal assignment of the human S1-5 gene (FBNL) that is highly homologous to fibrillin." Ikegawa S., Toda T., Okui K., Nakamura Y. Genomics 35:590-592(1996) [PubMed: 8812496] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Sequence, recombinant expression and tissue localization of two novel extracellular matrix proteins, fibulin-3 and fibulin-4." Giltay R., Timpl R., Kostka G. Matrix Biol. 18:469-480(1999) [PubMed: 10601734] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"EFEMP1 is not associated with sporadic early onset drusen." Sauer C.G., White K., Kellner U., Rudolph G., Jurklies B., Pauleikhoff D., Weber B.H. Ophthalmic Genet. 22:27-34(2001) [PubMed: 11262647] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Lung.
[6]	"A single EFEMP1 mutation associated with both malattia Leventinese and Doyne honeycomb retinal dystrophy." Stone E.M., Lotery A.J., Munier F.L., Heon E., Piguet B., Guymer R.H., Vandenburgh K., Cousin P., Nishimura D., Swiderski R.E., Silvestri G., Mackey D.A., Hagerman G.S., Bird A.C., Sheffield V.C., Schorderet D.F. Nat. Genet. 22:199-202(1999) [PubMed: 10369267] [Abstract] Cited for: VARIANT DHRD TRP-345, VARIANT PHE-220.
[7]	"Dominant radial drusen and Arg345Trp EFEMP1 mutation." Matsumoto M., Traboulsi E.I. Am. J. Ophthalmol. 131:810-812(2001) [PubMed: 11384588] [Abstract] Cited for: VARIANT DHRD TRP-345.
+	Additional computationally mapped references.

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Web resources

Mutations of the EFEMP1 gene

Retina International's Scientific Newsletter

GeneReviews

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Cross-references

Sequence databases
	U03877 mRNA. Translation: AAA65590.1. AY004330 AY004327 Genomic DNA. Translation: AAK11491.1. BC014410 mRNA. Translation: AAH14410.1. BC098561 mRNA. Translation: AAH98561.1.
IPI	IPI00029658. IPI00220813. IPI00220814. IPI00220815.
PIR	I38449.
RefSeq	NP_001034437.1. NP_001034438.1. NP_004096.2.
UniGene	Hs.76224
3D structure databases
HSSP	HSSP built from PDB template 1EMN based on UniProtKB P35555.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q12805. 6 interactions.
Proteomic databases
PRIDE	Q12805.
Genome annotation databases
Ensembl	ENSG00000115380. Homo sapiens. [Contig view]
GeneID	2202.
KEGG	hsa:2202.
UCSC	uc002rzh.1. human.
Organism-specific databases
GeneCards	GC02M056004.
H-InvDB	HIX0002067.
HGNC	HGNC:3218. EFEMP1.
MIM	126600. phenotype. 601548. gene.
Orphanet	99005. Doyne honeycomb retinal dystrophy (DHRD).
PharmGKB	PA27652.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q12805.
HOVERGEN	Q12805.
OMA	Q12805. VQTGRNN.
Gene expression databases
ArrayExpress	Q12805.
Bgee	Q12805.
CleanEx	HS_EFEMP1.
GermOnline	ENSG00000115380. Homo sapiens.
Family and domain databases
InterPro	IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_CS. IPR000742. EGF_3. IPR001881. EGF_Ca_bd. IPR013091. EGF_Ca_bd_2. IPR018097. EGF_Ca_bd_CS. [Graphical view]
Pfam	PF07645. EGF_CA. 6 hits. [Graphical view]
SMART	SM00179. EGF_CA. 4 hits. [Graphical view]
PROSITE	PS00010. ASX_HYDROXYL. 4 hits. PS00022. EGF_1. False negative. PS01186. EGF_2. 4 hits. PS50026. EGF_3. 4 hits. PS01187. EGF_CA. 6 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	8899.
SOURCE	Search...

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Entry information

Entry name

FBLN3_HUMAN

Accession

Primary (citable) accession number: Q12805
Secondary accession number(s): Q541U7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	July 7, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents