TNR21_HUMAN » Tumor necrosis factor receptor superfamily member 21

TNR21_HUMAN » Tumor necrosis factor receptor superfamily member 21
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
TNR21_HUMAN » Tumor necrosis factor receptor superfamily member 21 » Death receptor 6;
Hydrophobic Thickness 33.6 ± 1.5 Å
Tilt Angle 10 ± 4°
ΔGtransfer -28.5 kcal/mol
ΔGfold -24.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 349-371 (349-374)
Pathways

Cytokine-cytokine receptor interaction (KEGG)

PDB 2dbh (567-655), 3qo4 (A=42-218), 3u3p (A=42-348), 3u3q (A=42-348), 3u3s (A=42-348), 3u3t (A=42-348), 3u3v (A=42-348)
OPM none
Complexes none
Interactions

A4, Complex: A4:TNR21, PubMed

Domains

AA: 51-88, PDBID: 3QO4, Subunit A, Seq Identity:100%, TNFR/NGFR cysteine-rich region

AA: 91-131, PDBID: 3QO4, Subunit A, Seq Identity:100%, TNFR/NGFR cysteine-rich region

AA: 171-211, PDBID: 3QO4, Subunit A, Seq Identity:100%, TNFR/NGFR cysteine-rich region

AA: 417-498, PDBID: 1FAD, Subunit A, Seq Identity:33%, Death domain

UniProt annotation for TNR21_HUMAN » Tumor necrosis factor receptor superfamily member 21
FUNCTION: Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. Plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). N-APP binds TNFRSF21; this triggers caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase- 6). Negatively regulates oligodendrocyte survival, maturation and myelination. Plays a role in signaling cascades triggered by stimulation of T-cell receptors, in the adaptive immune response and in the regulation of T-cell differentiation and proliferation. Negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13 and IFNG by Th2 cells. Negatively regulates the production of IgG, IgM and IgM in response to antigens. May inhibit the activation of JNK in response to T-cell stimulation.

SUBUNIT: Interacts with N-APP (By similarity). Associates with TRADD. Interacts with NGFR.

TISSUE SPECIFICITY: Detected in fetal spinal cord and in brain neurons, with higher levels in brain from Alzheimer disease patients (at protein level). Highly expressed in heart, brain, placenta, pancreas, lymph node, thymus and prostate. Detected at lower levels in lung, skeletal muscle, kidney, testis, uterus, small intestine, colon, spleen, bone marrow and fetal liver. Very low levels were found in adult liver and peripheral blood leukocytes.

INDUCTION: Up-regulated by TNF.

UniProt features for TNR21_HUMAN » Tumor necrosis factor receptor superfamily member 21
SIGNAL 1 41 Potential.
CHAIN 42 655 Tumor necrosis factor receptor superfamily member 21.
REPEAT 50 88 TNFR-Cys 1.
REPEAT 90 131 TNFR-Cys 2.
REPEAT 133 167 TNFR-Cys 3.
REPEAT 170 211 TNFR-Cys 4.
DOMAIN 415 498 Death.
DISULFID 67 80 By similarity.
DISULFID 70 88 By similarity.
DISULFID 91 106 By similarity.
DISULFID 109 123 By similarity.
DISULFID 113 131 By similarity.
DISULFID 133 144 By similarity.
DISULFID 150 168 By similarity.
DISULFID 171 186 By similarity.
DISULFID 192 211 By similarity.
Amino Acid Sequence for TNR21_HUMAN » Tumor necrosis factor receptor superfamily member 21
MGTSPSSSTA LASCSRIARR ATATMIAGSL LLLGFLSTTT AQPEQKASNL IGTYRHVDRA TGQVLTCDKC PAGTYVSEHC TNTSLRVCSS CPVGTFTRHE NGIEKCHDCS QPCPWPMIEK LPCAALTDRE CTCPPGMFQS NATCAPHTVC PVGWGVRKKG TETEDVRCKQ CARGTFSDVP SSVMKCKAYT DCLSQNLVVI KPGTKETDNV CGTLPSFSSS TSPSPGTAIF PRPEHMETHE VPSSTYVPKG MNSTESNSSA SVRPKVLSSI QEGTVPDNTS SARGKEDVNK TLPNLQVVNH QQGPHHRHIL KLLPSMEATG GEKSSTPIKG PKRGHPRQNL HKHFDINEHL PWMIVLFLLL VLVVIVVCSI RKSSRTLKKG PRQDPSAIVE KAGLKKSMTP TQNREKWIYY CNGHGIDILK LVAAQVGSQW KDIYQFLCNA SEREVAAFSN GYTADHERAY AALQHWTIRG PEASLAQLIS ALRQHRRNDV VEKIRGLMED TTQLETDKLA LPMSPSPLSP SPIPSPNAKL ENSALLTVEP SPQDKNKGFF VDESEPLLRC DSTSSGSSAL SRNGSFITKE KKDTVLRQVR LDPCDLQPIF DDMLHFLNPE ELRVIEEIPQ AEDKLDRLFE IIGVKSQEAS QTLLDSVYSH LPDLL