EPHB4 EPH receptor B4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EPHB4provided by HGNC
Official Full Name: EPH receptor B4provided by HGNC
Primary source: HGNC:HGNC:3395
See related: Ensembl:ENSG00000196411 MIM:600011; AllianceGenome:HGNC:3395
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: HTK; MYK1; HFASD; CMAVM2; LMPHM7; TYRO11
Summary: Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in placenta (RPKM 28.2), endometrium (RPKM 22.9) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q22.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (100802565..100827523, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (102042646..102067608, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (100400187..100425145, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology.
Title: SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology.
Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation and Novel Mutations in Cerebral Cavernous Malformations: In Vitro and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell Pathophysiology.
Title: Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation and Novel Mutations in Cerebral Cavernous Malformations: In Vitro and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell Pathophysiology.
Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
Title: Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with EPHB4 pathogenic variants.
Title: Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with EPHB4 pathogenic variants.
Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.
Title: Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.
Mutations in EPHB4 cause human venous valve aplasia.
Title: Mutations in EPHB4 cause human venous valve aplasia.
EphrinB2-EphB4 Signaling in Neurooncological Disease.
Title: EphrinB2-EphB4 Signaling in Neurooncological Disease.
EPHB4 mutation causes adult and adolescent-onset primary lymphedema.
Title: EPHB4 mutation causes adult and adolescent-onset primary lymphedema.
Transcriptional and Post-Translational Control Mechanisms for EphB4 Expression in Physiology and Cancer Disease.
Title: Transcriptional and Post-Translational Control Mechanisms for EphB4 Expression in Physiology and Cancer Disease.
Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion.
Title: Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion.

Submit: New GeneRIF Correction See all GeneRIFs (135)

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
Capillary malformation-arteriovenous malformation 2 MedGen: C4748670 OMIM: 618196 GeneReviews: Capillary Malformation-Arteriovenous Malformation Syndrome	Compare labs
Capillary malformation-arteriovenous malformation syndrome MedGen: C1842180 GeneReviews: Capillary Malformation-Arteriovenous Malformation Syndrome	Compare labs
Lymphatic malformation 7 MedGen: C4310629 OMIM: 617300 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation. 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

D7S2738 (e-PCR)
- UniSTS:80152

D7S2738 (e-PCR)
- UniSTS:11301

EPHB4_612 (e-PCR)
- UniSTS:277214

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ephrin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane receptor protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in cell migration involved in sprouting angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in ephrin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ephrin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in heart morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: ephrin type-B receptor 4

Names: ephrin receptor EphB4; hepatoma transmembrane kinase; tyrosine-protein kinase TYRO11; tyrosine-protein kinase receptor HTK

NP_004435.3

EC 2.7.10.1

XP_016867305.1

EC 2.7.10.1

XP_054213436.1

EC 2.7.10.1

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_052671.1 RefSeqGene

Range

4999..29957

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004444.5 → NP_004435.3 ephrin type-B receptor 4 precursor

See identical proteins and their annotated locations for NP_004435.3

Status: REVIEWED

Source sequence(s)

AC011895, AY056048, BC052804, CB962032

Consensus CDS

CCDS5706.1

UniProtKB/Swiss-Prot

B5A970, B5A971, B5A972, P54760, Q7Z635, Q9BTA5, Q9BXP0

UniProtKB/TrEMBL

Q541P7, Q59F17

Related

ENSP00000350896.3, ENST00000358173.8

Conserved Domains (5) summary

cd05065
Location:610 → 878

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09554
Location:907 → 973

SAM_EPH-B4; SAM domain of EPH-B4 subfamily of tyrosine kinase receptors

cd10474
Location:17 → 196

EphR_LBD_B4; Ligand Binding Domain of Ephrin type-B Receptor 4

cd00063
Location:434 → 526

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam14575
Location:564 → 610

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

100802565..100827523 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017011816.2 → XP_016867305.1 ephrin type-B receptor 4 isoform X1

UniProtKB/TrEMBL

Q59F17

Conserved Domains (7) summary

cd05065
Location:628 → 896

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09554
Location:925 → 991

SAM_EPH-B4; SAM domain of EPH-B4 subfamily of tyrosine kinase receptors

smart00454
Location:922 → 989

SAM; Sterile alpha motif

cd10474
Location:17 → 196

EphR_LBD_B4; Ligand Binding Domain of Ephrin type-B Receptor 4

cd00063
Location:452 → 544

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam07714
Location:633 → 892

Pkinase_Tyr; Protein tyrosine kinase

pfam14575
Location:582 → 628

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain