MEGF8 (19q13.2) , 12 kelch-toistoa, monta EGF-kaltaista domaania, ec domaanin CUB , plasmod Pvs28 ja vWFA domaanit omaava iso proteiini

https://www.ncbi.nlm.nih.gov/gene/1954
(En ole tavannut aiemmin sellaista proteiinia tästä  Kelch-superperheestä, jossa olisi näin monta kelch-toistoa(12).  Onkohan se geenirekombinaatio  jokin hybridi fylogeneettisesti kun siinä on kahden  Kelch-proteiini verran kelch-domeeneja ? Katson jos löydän fylogeneettistä tietoa)

Peptidisekvenssi on 2845 aa.  Proteiinilla on extrasellulaarinen CUB-domeeni (a.a. 49-1399 , N terminaalin lähellä. Transmembraaninen jakso on C-terminaalissa (2648-2845 a.a.)  EGF-kaltaisia domeeneja on useita. Löytyy myös PSI,  plexiinitoisto (A.A. 950- 988)  ja Plasmod-Pvs28 domeeni (a.a. 2189-2314 ) (plasmodium ookineetin pintaproteiini, jonka kaltaisesta on  kehitelty  rokotetta plasmodium vivaxtyyppiä vastaan). Sitten löytyy von Willebrand faktoriA- tyyppinen domeeni, jonka kaltaista alunperin havaittiin  hyytymistekijöistä.
 Kelch-toistot  kelch-3 ja Kelch neljä ovat  galaktoosioksidaasidomeeneja.
Geeniä ilmenee  runsaiten aivossa ja rasvakudoksessa. Sen puutteet  tunnetaan kliinisenä  oireyhtymänä Carpenter syndroma 2:na,  jossa on mm.  kehon lateralisaatiomallin  muuttumisia,kuten sydän oikealla puolella.https://www.norio-keskus.fi/tietoa/diagnoosikohtaista-tietoa/carpenterin-oireyhtyma.html
Carpenterin oireyhtymätyyppi 1:n geneettinen poikkeavuus on paikannettu kromosomiin 6 (6p12.1-p11.2), RAB23-nimiseen geeniin. Carpenterin oireyhtymän tyyppi 2 aiheutuu puolestaan MEGF8-geenin mutaatiosta kromosomissa 19 (19q13.2).
Molemmat Carpenterin oireyhtymätyypit noudattavat autosomissa resessiivistä eli peittyvää periytymistapaa.
Carpenterin oireyhtymän tyyppi 1 on yleisempi kuin tyyppi 2. Carpenterin oireyhtymän kokonaisesiintyvyydeksi on arvioitu 1 : 1 000 000. Lääketieteellinen kirjallisuus kuvaa yli 70 potilasta. Kaikissa tapauksissa vanhemmat ovat olleet terveitä, mikä viittaa oireyhtymän syntyneen biologisesti sattumalta, aivan uuden, nk. de novo-mutaation seurauksesta. De novo-mutaatiot saavat alkunsa hedelmöitykseen osallistuvan sukusolun, munasolun tai siittiön, kypsyessä tai alkion varhaisten solunjakautumisten yhteydessä pian hedelmöityksen jälkeen.

Official Full Name

multiple EGF like domains 8

Also known as

SBP1; CRPT2; EGFL4; C19orf49
CRPT2 ( Carpenter syndrome 2)

Summary

The protein encoded by this gene is a single-pass type I membrane protein of unknown function that contains several EGF-like domains, Kelch repeats, and PSI domains. Defects in this gene are a cause of Carpenter syndrome 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

Expression

Ubiquitous expression in brain (RPKM 10.9), fat (RPKM 6.9) and 25 other tissues See more

Preferred Names

multiple epidermal growth factor-like domains protein 8

Names

EGF-like domain-containing protein 4

EGF-like-domain, multiple 4

HBV pre-S2-binding protein 1

HBV pre-s2 binding protein 1

epidermal growth factor-like protein 4

hepatitis B virus pre-S2-binding protein 1

.

1. [Screening of the genes of hepatitis B virus PreS2 interacting proteins]. Lu YY, et al. Zhonghua Gan Zang Bing Za Zhi, 2003 Jan. PMID 12546731
2. Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization. Twigg SR, et al. Am J Hum Genet, 2012 Nov 2. PMID 23063620, Free PMC Article
3. Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening. Nakayama M, et al. Genomics, 1998 Jul 1. PMID 9693030
4. Role of the E3 ubiquitin ligase RNF157 as a novel downstream effector linking PI3K and MAPK signaling pathways to the cell cycle. Dogan T, et al. J Biol Chem, 2017 Sep 1. PMID 28655764, Free PMC Article
5. Comparison of an expanded ataxia interactome with patient medical records reveals a relationship between macular degeneration and ataxia. Kahle JJ, et al. Hum Mol Genet, 2011 Feb 1. PMID 21078624, Free PMC Article

See all (19) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

1. mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members.

 NP_001258867.1  multiple epidermal growth factor-like domains protein 8 isoform 1 precursor
See identical proteins and their annotated locations for NP_001258867.1

Status: REVIEWED

Description

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

Conserved Domains (9) summary

cd00041
Location:49 → 139

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00055
Location:1210 → 1259

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

sd00038
Location:228 → 275

Kelch; KELCH repeat [structural motif]

pfam01437
Location:950 → 998

PSI; Plexin repeat.A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin. Two copies of the repeat are found in mahogany protein. A related C. elegans protein contains four copies of the repeat. The Met receptor contains a single copy of the repeat. The Pfam alignment shows 6 conserved cysteine residues that may form three conserved disulphide bridges, whereas shows 8 conserved cysteines. The pattern of conservation suggests that cysteines 5 and 7 (that are not absolutely conserved) form a disulphide bridge (Personal observation. A Bateman).

pfam06247
Location:2189 → 2314

Plasmod_Pvs28; Plasmodium ookinete surface protein Pvs28This family consists of several ookinete surface proteins (Pvs28) from several species of Plasmodium. Pvs25 and Pvs28 are expressed on the surface of ookinetes. These proteins are potential candidates for vaccine and induce antibodies that block the infectivity of Plasmodium vivax in immunised animals.

pfam12947
Location:1078 → 1112

EGF_3; EGF domain

pfam13415
Location:1630 → 1680

Kelch_3; Galactose oxidase, central domain

pfam13418
Location:227 → 276

Kelch_4; Galactose oxidase, central domain

cl00057
Location:1011 → 1035

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 fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains....