EH domain-containing protein 1 (EHD1)

The protein contains 534 amino acids for an estimated molecular weight of 60627 Da.

 

ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis. In vitro causes vesiculation of endocytic membranes (PubMed:24019528). Acts in early endocytic membrane fusion and membrane trafficking of recycling endosomes (PubMed:15020713, PubMed:17233914, PubMed:20801876). Recruited to endosomal membranes upon nerve growth factor stimulation, indirectly regulates neurite outgrowth (By similarity). Plays a role in myoblast fusion (By similarity). Involved in the unidirectional retrograde dendritic transport of endocytosed BACE1 and in efficient sorting of BACE1 to axons implicating a function in neuronal APP processing (By similarity). Plays a role in the formation of the ciliary vesicle (CV), an early step in cilium biogenesis. Proposed to be required for the fusion of distal appendage vesicles (DAVs) to form the CV by recruiting SNARE complex component SNAP29. Is required for recruitment of transition zone proteins CEP290, RPGRIP1L, TMEM67 and B9D2, and of IFT20 following DAV reorganization before Rab8-dependent ciliary membrane extension. Required for the loss of CCP110 form the mother centriole essential for the maturation of the basal body during ciliogenesis (PubMed:25686250). (updated: Oct. 25, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 0

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The reference OMIM entry for this protein is 605888

Eh domain-containing 1; ehd1

DESCRIPTION

The EH domain-containing-1 gene belongs to a highly conserved gene family encoding eps15 homology (EH) domain-containing proteins. The protein-binding EH domain has approximately 100 residues and was first noted in Eps15 (600051), a substrate for the epidermal growth factor receptor. The EH domain has been shown to be an important motif in proteins involved in protein-protein interactions and in intracellular sorting (Di Fiore et al., 1997).

CLONING

By screening a human cerebellar cDNA library with a mouse genomic fragment, Mintz et al. (1999) isolated a cDNA which was then used as a probe to screen a mouse brain cDNA library. The sequences of the deduced human and mouse proteins, designated EHD1, contain 534 amino acids and share approximately 94% homology. Both proteins have an EH domain, including an EF-Ca(2+)-binding motif, at their C terminus, a highly conserved ATP/GTP-binding domain, and a central coiled-coil structure. Cotransfection experiments indicated that the human EHD1 protein has a molecular mass of 62 kD. Northern blot analysis indicated the existence of 2 EHD1 RNA species in mouse and 3 in human (2.0, 3.2, 3.6 kb). In mouse, both transcripts are highly expressed in testis and are present in kidney, heart, intestine, and brain. In human, the smallest transcript is predominant in testis, while the largest transcript is present in other tissues as well. RT-PCR analysis indicated that the 3.2-kb mRNA results from skipping of exon 3. Subcellular localization experiments indicated that EHD1 colocalizes with transferrin (190000)-containing endocytic vesicles. EHD1 was also present in other cellular structures, including the Golgi apparatus. Immunohistochemical analyses in mice demonstrated EHD1 expression in male germ cells, in adipocytes, in several retinal layers, and, to a lesser extent, in uterus, skeletal muscle, and kidney. In situ hybridization and immunohistochemical analyses indicated that Ehd1 was expressed by day 9.5 in the limb buds and pharyngeal arches and at day 10.5 in sclerotomes, at various elements of the branchial apparatus, and in the occipital region. At day 15.5 Ehd1 expression peaked in cartilage, preceding hypertrophy and ossification, and at day 17.5 there was no expression in the bones.

GENE FUNCTION

Rotem-Yehudar et al. (2001) found evidence for a role for EHD1 in the endocytosis of IGF1 receptors (IGF1R; 147370). Through immunoprecipitation of rat tissues, they found that EHD1 interacts directly with the synaptosomal-associated protein SNAP29 (604202) and that both are present in complexes with IGF1R. They also found that IGF1 induction of EHD1-transfected CHO cells results in intracellular colocalization of EHD1 and IGF1R. By immunofluorescence microscopy of HeLa cells, Naslavsky et al. (2004) detected EHD1 partly colocalized with rabenosyn-5 (ZFYVE20; 609511) in vesicular and tubular structures. Depletion of either EHD1 or rabenosyn-5 in HeLa cells by RNA interference (RNAi) delayed recycling of transferrin and major histocompatibility complex class I (see HLA-A; 142800) to the plasma membrane. Depletion of EHD1 caused accumulation of internalized cargo in a compact juxtanuclear compartment, but depletion of rabenosyn-5 caused retention of cargo within a dispersed peripheral compartment. Simultaneous depletion of both rabenosyn-5 and EHD1 resulted in a phenotype similar to that observed with rabenosyn-5 RNAi alone, suggesting that rabenosyn-5 acts befo ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605888 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed