NEX-1 (Caenorhabditis elegans)
Description [+]
- Synonyms: NEX-1,
- Species: Metazoa;Bilateria;Ecdysozoa;Nematoda; Caenorhabditis elegans
- Short gene description: nex-1 encodes an annexin, a member of a family of calcium-dependent phospholipid binding proteins. NEX-1 is required for efficient engulfment of apoptotic cell corpses in the pharynx, and may also function in other membrane fusion events, such as exocytosis. NEX-1 in vitro can bind phosphatidylserine, phosphatidylinositol, heparin, heparan sulfate, and chondroitin sulfate. NEX-1 is expressed in the pharynx, hypodermal cells, the vulva, the uterus, the spermathecal valve, and yolk granules of maturing oocytes. [Source: WormBase]
- Family: other
- Process: apoptosis,
- Pathways: apoptotic cell clearance,
- Criteria: manually curated
- Curator comment: Null
- Human ortholog(s): ANXA1 ANXA13 ANXA5 ANXA8 ANXA6 ANXA4 ANXA8L1 ANXA11 ANXA8L2 ANXA7
- WIKI: NEX-1-C_elegans
References [+]
- Annexin I is an endogenous ligand that mediates apoptotic cell engulfment.
- Arur S, Uche UE, Rezaul K, Fong M, Scranton V, Cowan AE, Mohler W, Han DK
- Engulfment of apoptotic cells requires presentation of new cell surface ligands by the dying cells. Using a differential proteomics technology, we identify that annexin I is a caspase-dependent engulfment ligand; it is recruited from the cytosol and exported to the outer plasma membrane leaflet, colocalizes with phosphatidylserine, and is required for efficient clearance of apoptotic cells. Furthermore, phosphatidylserine receptor (PSR) clustering around apoptotic cells indicates a requirement for annexin I. In the nematode Caenorhabditis elegans, downregulation of the annexin homolog prevents efficient engulfment of pharyngeal cell corpses. These results provide novel mechanistic insights into how apoptotic cells are removed and may explain a pathogenic mechanism of chronic inflammatory diseases where annexin I autoantibodies have been described. Dev Cell. 2003 Apr;4(4):587-98.
- Tales of cannibalism, suicide, and murder: Programmed cell death in C. elegans.
- Kinchen JM, Hengartner MO
- Life is pleasant. Death is peaceful. It's the transition that's troublesome, said Isaac Asimov. Indeed, much scientific work over the last hundred years centered around attempts either to stave off or to induce the onset of death, at both the organismal and the cellular levels. In this quest, the nematode C. elegans has proven an invaluable tool, first, in the articulation of the genetic pathway by which programmed cell death proceeds, and also as a continuing source of inspiration. It is our purpose in this Chapter to familiarize the reader with the topic of programmed cell death in C. elegans and its relevance to current research in the fields of apoptosis and cell corpse clearance. Curr Top Dev Biol. 2005;65:1-45.
- References from Human ortholog(s):
- Annexin-1 and peptide derivatives are released by apoptotic cells and stimulate phagocytosis of apoptotic neutrophils by macrophages.
- Scannell M, Flanagan MB, deStefani A, Wynne KJ, Cagney G, Godson C, Maderna P
- The resolution of inflammation is a dynamically regulated process that may be subverted in many pathological conditions. Macrophage (Mphi) phagocytic clearance of apoptotic leukocytes plays an important role in the resolution of inflammation as this process prevents the exposure of tissues at the inflammatory site to the noxious contents of lytic cells. It is increasingly appreciated that endogenously produced mediators, such as lipoxins, act as potent regulators (nanomolar range) of the phagocytic clearance of apoptotic cells. In this study, we have investigated the intriguing possibility that apoptotic cells release signals that promote their clearance by phagocytes. We report that conditioned medium from apoptotic human polymorphonuclear neutrophils (PMN), Jurkat T lymphocytes, and human mesangial cells promote phagocytosis of apoptotic PMN by Mphi and THP-1 cells differentiated to a Mphi-like phenotype. This prophagocytic activity appears to be dose dependent, sensitive to the caspase inhibitor zVAD-fmk, and is associated with actin rearrangement and release of TGF-beta1, but not IL-8. The prophagocytic effect can be blocked by the formyl peptide receptor antagonist Boc2, suggesting that the prophagocytic factor(s) may interact with the lipoxin A(4) receptor, FPRL-1. Using nanoelectrospray liquid chromatography mass spectrometry and immunodepletion and immunoneutralization studies, we have ascertained that annexin-1 and peptide derivatives are putative prophagocytic factors released by apoptotic cells that promote phagocytosis of apoptotic PMN by M[phi] and differentiated THP-1 cells. These data highlight the role of annexin-1 and peptide derivatives in promoting the resolution of inflammation and expand on the therapeutic anti-inflammatory potential of annexin-1. J Immunol. 2007 Apr 1;178(7):4595-605.
- Apoptosis: controlled demolition at the cellular level.
- Taylor RC, Cullen SP, Martin SJ
- Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses. Much of what happens during the demolition phase of apoptosis is orchestrated by members of the caspase family of cysteine proteases. These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules. Nat Rev Mol Cell Biol. 2008 Mar;9(3):231-41.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Annexin1881 | 18 | 81 |
| PFAM A | Annexin1881 | 88 | 153 |
| PFAM A | Annexin1881 | 171 | 238 |
| PFAM A | Annexin1881 | 248 | 313 |
Protein sequence [+]
nex-1 | Caenorhabditis elegans | 6239 | length:322
MTSPYATIVDAREFNAPMFAEKIDRALRAGEKDAVVNVITSISNAQRQQLREPYKLKYGK
DIIQALDKKFSGDLEKAIFALMETPLDYDVKQLKAAMKGLGTDEAVLIEILCSRTVDQLR
AIRVTYEKEYGKALEADIAGDTSGEFRDLLVSLVTGSKDGSHDTNDAQAKDDAVRLFADG
KAKLAKKDGTHFLHILATQNQYQLRKVFAYFQELAGGSIEKSIEKEFSGDLQKSYLTIVR
AASDKQKFFAQQLHASMKGLGTRDNDLIRVIVTRSEVDLELIKAEFQELYSKSLADTVKG
DTSGAYRDALLSIINGNHATAH
DIIQALDKKFSGDLEKAIFALMETPLDYDVKQLKAAMKGLGTDEAVLIEILCSRTVDQLR
AIRVTYEKEYGKALEADIAGDTSGEFRDLLVSLVTGSKDGSHDTNDAQAKDDAVRLFADG
KAKLAKKDGTHFLHILATQNQYQLRKVFAYFQELAGGSIEKSIEKEFSGDLQKSYLTIVR
AASDKQKFFAQQLHASMKGLGTRDNDLIRVIVTRSEVDLELIKAEFQELYSKSLADTVKG
DTSGAYRDALLSIINGNHATAH
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL005408-PA | orthology | Aedes |
| A_aegypti_AAEL005417-PA | orthology | Aedes |
| A_aegypti_AAEL005426-PA | orthology | Aedes |
| A_aegypti_AAEL011302-PB | orthology | Aedes |
| A_gambiae_AGAP003720-PA | orthology | Anopheles |
| A_gambiae_AGAP003721-PA | orthology | Anopheles |
| A_gambiae_AGAP003722-PA | orthology | Anopheles |
| ANXA6_CHICK | orthology | Chicken |
| IPI00596627.4 | orthology | Chicken |
| IPI00585409.1 | orthology | Chicken |
| IPI00810765.1 | orthology | Chicken |
| ANXA2_CHICK | orthology | Chicken |
| NP_001012921.1 | orthology | Chicken |
| ANXA11 | orthology | Chimpanzee |
| ANXA4 | orthology | Chimpanzee |
| ANXA5_PANTR | orthology | Chimpanzee |
| ANXA13 | orthology | Chimpanzee |
| ANXA8_PANTR | orthology | Chimpanzee |
| ANXA6 | orthology | Chimpanzee |
| ANXA1_PANTR | orthology | Chimpanzee |
| XR_024382.1 | orthology | Chimpanzee |
| ANXA7 | orthology | Chimpanzee |
| ANXA4_BOVIN | orthology | Cow |
| NP_001098905.1 | orthology | Cow |
| ANXA2_BOVIN | orthology | Cow |
| ANXA6_BOVIN | orthology | Cow |
| ANX11_BOVIN | orthology | Cow |
| ANXA5_BOVIN | orthology | Cow |
| ANXA8_BOVIN | orthology | Cow |
| ANXA7_BOVIN | orthology | Cow |
| XM_536412.2 | orthology | Dog |
| ANXA6 | orthology | Dog |
| ANXA7 | orthology | Dog |
| ANX13_CANFA | orthology | Dog |
| ANXA5 | orthology | Dog |
| ANXA11 | orthology | Dog |
| AnnX | orthology | Fly |
| Anxb11 | orthology | Fly |
| ANXA11 (1 of 2) | orthology | Fugu |
| ANXA4 | orthology | Fugu |
| ANXA13 (2 of 2) | orthology | Fugu |
| ANXA6 | orthology | Fugu |
| ANXA11 (2 of 2) | orthology | Fugu |
| ANXA5 (1 of 2) | orthology | Fugu |
| ANXA11 (1 of 2) | orthology | Gasterosteus |
| ANXA13 (1 of 2) | orthology | Gasterosteus |
| ANXA5 (1 of 2) | orthology | Gasterosteus |
| ANXA4 | orthology | Gasterosteus |
| ANXA5 (2 of 2) | orthology | Gasterosteus |
| ANXA6 | orthology | Gasterosteus |
| G_gorilla_ENSGGOP00000005013 | orthology | Gorilla |
| ANXA11 | orthology | Gorilla |
| G_gorilla_ENSGGOP00000012435 | orthology | Gorilla |
| ANXA5 | orthology | Horse |
| ANXA4 | orthology | Horse |
| ANXA7 | orthology | Horse |
| ANXA11 | orthology | Horse |
| XP_001500744.1 | orthology | Horse |
| ANXA13 | orthology | Horse |
| ANXA6 | orthology | Horse |
| ANXA1 | orthology | Human |
| ANXA13 | orthology | Human |
| ANXA5 | orthology | Human |
| ANXA8 | orthology | Human |
| ANXA6 | orthology | Human |
| ANXA4 | orthology | Human |
| ANXA8L1 | orthology | Human |
| ANXA11 | orthology | Human |
| ANXA8L2 | orthology | Human |
| ANXA7 | orthology | Human |
| ANXA11 | orthology | Lyzard |
| A_carolinensis_ENSACAP00000009701 | orthology | Lyzard |
| ANXA7 | orthology | Lyzard |
| ANXA6 | orthology | Lyzard |
| ANXA4 | orthology | Macaca |
| ANXA5 | orthology | Macaca |
| ANXA2 | orthology | Macaca |
| XM_001083294.1 | orthology | Macaca |
| ANXA13 | orthology | Macaca |
| ANXA11 | orthology | Macaca |
| ANXA6 | orthology | Macaca |
| Q7M2V1_MACMU | orthology | Macaca |
| ANXA11 (2 of 2) | orthology | Medaka |
| ANXA6 | orthology | Medaka |
| O93445_ORYLA | orthology | Medaka |
| O93444_ORYLA | orthology | Medaka |
| O93447_ORYLA | orthology | Medaka |
| ANXA13 (1 of 2) | orthology | Medaka |
| ANXA7 | orthology | Monodelphis |
| ANXA11 | orthology | Monodelphis |
| XM_001371763.1 | orthology | Monodelphis |
| ANXA6 | orthology | Monodelphis |
| ANXA4 | orthology | Monodelphis |
| Anxa11 | orthology | Mouse |
| Anxa8 | orthology | Mouse |
| Anxa5 | orthology | Mouse |
| Anxa2 | orthology | Mouse |
| AC152395.9 | orthology | Mouse |
| Anxa7 | orthology | Mouse |
| Anxa6 | orthology | Mouse |
| Anxa4 | orthology | Mouse |
| P_pygmaeus_ENSPPYP00000002609 | orthology | Orangutan |
| ANXA11 | orthology | Orangutan |
| ANXA7 | orthology | Orangutan |
| ANXA2_PONPY | orthology | Orangutan |
| ANXA4 | orthology | Orangutan |
| ANXA5 | orthology | Orangutan |
| ANXA6 | orthology | Orangutan |
| ANXA13 | orthology | Orangutan |
| ANXA1_PONPY | orthology | Orangutan |
| O_anatinus_ENSOANP00000016920 | orthology | Ornithorhynchus |
| ANXA13 | orthology | Ornithorhynchus |
| ANXA7 | orthology | Ornithorhynchus |
| ANXA6 | orthology | Rabbit |
| ANXA13 | orthology | Rabbit |
| ANXA4 | orthology | Rabbit |
| NP_001011918.1 | orthology | Rat |
| ANXA5_RAT | orthology | Rat |
| ANXA4_RAT | orthology | Rat |
| ANXA8_RAT | orthology | Rat |
| ANXA2_RAT | orthology | Rat |
| NP_569100.2 | orthology | Rat |
| NP_001128382.1 | orthology | Rat |
| ANXA6_RAT | orthology | Rat |
| ANXA5 (1 of 2) | orthology | Tetraodon |
| ANXA11 (1 of 3) | orthology | Tetraodon |
| ANXA6 | orthology | Tetraodon |
| ANXA4 | orthology | Tetraodon |
| ANXA5 (2 of 2) | orthology | Tetraodon |
| ANXA11 (2 of 3) | orthology | Tetraodon |
| ANXA11 (3 of 3) | orthology | Tetraodon |
| anxa4 | orthology | Xenopus |
| anxa5 | orthology | Xenopus |
| anxa13 | orthology | Xenopus |
| anxa7 | orthology | Xenopus |
| ANXA6 | orthology | Zebra finch |
| ANXA4 | orthology | Zebra finch |
| ANXA2 | orthology | Zebra finch |
| ANXA11 | orthology | Zebra finch |
| ANXA7 | orthology | Zebra finch |
| ANXA8L1 | orthology | Zebra finch |
| ANXA13 | orthology | Zebra finch |
| anxa5b | orthology | Zebrafish |
| anxa13 | orthology | Zebrafish |
| anxa4 | orthology | Zebrafish |
| anxa11a | orthology | Zebrafish |
| anxa11b | orthology | Zebrafish |
| nex-3 | paralogy | Worm |
| nex-2 | paralogy | Worm |
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