EFEMP2 EGF containing fibulin extracellular matrix protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EFEMP2provided by HGNC
Official Full Name: EGF containing fibulin extracellular matrix protein 2provided by HGNC
Primary source: HGNC:HGNC:3219
See related: Ensembl:ENSG00000172638 MIM:604633; AllianceGenome:HGNC:3219
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MBP1; UPH1; FBLN4; ARCL1B
Summary: A large number of extracellular matrix proteins have been found to contain variations of the epidermal growth factor (EGF) domain and have been implicated in functions as diverse as blood coagulation, activation of complement and determination of cell fate during development. The protein encoded by this gene contains four EGF2 domains and six calcium-binding EGF2 domains. This gene is necessary for elastic fiber formation and connective tissue development. Defects in this gene are cause of an autosomal recessive cutis laxa syndrome. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]
Expression: Ubiquitous expression in ovary (RPKM 37.0), endometrium (RPKM 33.0) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.1

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (65866441..65872800, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (65860912..65867272, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (65633912..65640271, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Whole-exome sequencing uncovers a novel EFEMP2 gene variant (c.C247T) associated with dominant nonsyndromic thoracic aortic aneurysm.
Title: Whole-exome sequencing uncovers a novel EFEMP2 gene variant (c.C247T) associated with dominant nonsyndromic thoracic aortic aneurysm.
EFEMP2 upregulates PD-L1 expression via EGFR/ERK1/2/c-Jun signaling to promote the invasion of ovarian cancer cells.
Title: EFEMP2 upregulates PD-L1 expression via EGFR/ERK1/2/c-Jun signaling to promote the invasion of ovarian cancer cells.
Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.
Title: Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.
STEAP2 promotes osteosarcoma progression by inducing epithelial-mesenchymal transition via the PI3K/AKT/mTOR signaling pathway and is regulated by EFEMP2.
Title: STEAP2 promotes osteosarcoma progression by inducing epithelial-mesenchymal transition via the PI3K/AKT/mTOR signaling pathway and is regulated by EFEMP2.
EFEMP2 increases the invasion ability of cervical cancer cells by promoting EMT via the Raf/MEK/ERK signaling pathway.
Title: EFEMP2 increases the invasion ability of cervical cancer cells by promoting EMT via the Raf/MEK/ERK signaling pathway.
Downregulation of fibulin-4 inhibits autophagy and promotes the sensitivity of esophageal squamous cell carcinoma cells to apatinib by activating the Akt-mTOR signaling pathway.
Title: Downregulation of fibulin-4 inhibits autophagy and promotes the sensitivity of esophageal squamous cell carcinoma cells to apatinib by activating the Akt-mTOR signaling pathway.
EFEMP2 indicates assembly of M0 macrophage and more malignant phenotypes of glioma.
Title: EFEMP2 indicates assembly of M0 macrophage and more malignant phenotypes of glioma.
These results may explain the changes in protease cleavage sites, reduced secretion and impaired extracellular assembly of the E126K and D203A fibulin-4 mutants and provide further insight into understanding the molecular basis of the associated clinical phenotypes.
Title: Molecular dynamics simulations on human fibulin-4 mutants D203A and E126K reveal conformational changes in EGF domains potentially responsible for enhanced protease lability and impaired extracellular matrix assembly.
These results are consistent with a role of FBLN2 in mammary epithelial basement membrane stability, and that its down-regulation in breast cancer is associated with loss of the basement membrane and early invasion.
Title: Fibulin-2 is required for basement membrane integrity of mammary epithelium.
different mutations in the fibulin-4 gene result in different molecular defects affecting secretion rates, protein stability, LOX-induced cross-linking, or binding to other ECM components and molecules of the TGF-beta pathway.
Title: Functional consequence of fibulin-4 missense mutations associated with vascular and skeletal abnormalities and cutis laxa.

Submit: New GeneRIF Correction See all GeneRIFs (33)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cutis laxa, autosomal recessive, type 1B MedGen: C3280798 OMIM: 614437 GeneReviews: EFEMP2-Related Cutis Laxa	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-18484 (e-PCR)
- UniSTS:23557

RH36142 (e-PCR)
- UniSTS:23583

IB1075 (e-PCR)
- UniSTS:29253

D11S2297E (e-PCR)
- UniSTS:45930

STS-H53813 (e-PCR)
- UniSTS:36463

STS-R09524 (e-PCR)
- UniSTS:52990

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables extracellular matrix structural constituent	RCA inferred from Reviewed Computational Analysis more info	PubMed
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in aorta development	ISS Inferred from Sequence or Structural Similarity more info
involved_in aorta smooth muscle tissue morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in elastic fiber assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in elastic fiber assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of vascular associated smooth muscle cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of aortic smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of collagen fibril organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of smooth muscle cell-matrix adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of collagen fibril organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in vascular associated smooth muscle cell development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in basement membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in elastic fiber	IDA Inferred from Direct Assay more info	PubMed
located_in elastic fiber	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular matrix	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular vesicle	HDA more info	PubMed
located_in microfibril	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: EGF-containing fibulin-like extracellular matrix protein 2

Names: EGF containing fibulin like extracellular matrix protein 2; FIBL-4; fibulin 4; mutant p53 binding protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012304.2 RefSeqGene

Range

5135..11494

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_016938.5 → NP_058634.4 EGF-containing fibulin-like extracellular matrix protein 2 precursor

See identical proteins and their annotated locations for NP_058634.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the functional protein.

Source sequence(s)

AF124486, BC010456, BC018871, BP382163, BQ478413

Consensus CDS

CCDS8116.1

UniProtKB/Swiss-Prot

A8K7R4, B3KM31, B3KQT1, O75967, O95967

UniProtKB/TrEMBL

B2RCM5, Q6FH22, Q96TF5

Related

ENSP00000309953.6, ENST00000307998.11

Conserved Domains (3) summary

smart00179
Location:123 → 163

EGF_CA; Calcium-binding EGF-like domain

cl00057
Location:241 → 276

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

cl21504
Location:283 → 310

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

RNA

NR_037718.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an internal segment, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC010456, BC018871, BP382163, BQ478413

Related

ENST00000528176.5