TNF receptor-associated factor 2 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''TRAF2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and

TRAF1 TNF receptor-associated factor 1 is a protein that in humans is encoded by the ''TRAF1'' gene. Function The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate wit ...

interacts with the IAP family members

cIAP1 cIAP1 (also named BIRC2) is the abbreviation for a human protein, cellular inhibitor of apoptosis protein-1. It belongs to the IAP family of proteins and therefore contains at least one BIR ( baculoviral IAP repeat) domain. cIAP1 is a multi-functi ...

and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of

caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cystei ...

activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined.

Interactions

TRAF2 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

ASK1 Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and ...

, *

BCL10 B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the ''BCL10'' gene. Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma. Function Bcl10 was identified by its translocation in a case of ...

, *

BIRC2 Baculoviral IAP repeat-containing protein 2 (also known as cIAP1) is a protein that in humans is encoded by the ''BIRC2'' gene. Function cIAP1 is a member of the Inhibitor of Apoptosis family that inhibit apoptosis by interfering with the acti ...

, *

Baculoviral IAP repeat-containing protein 3 Baculoviral IAP repeat-containing protein3 (also known as cIAP2) is a protein that in humans is encoded by the ''BIRC3'' gene. cIAP2 is a member of the inhibitor of apoptosis family that inhibit apoptosis by interfering with the activation of cas ...

, * CASP8AP2, *

CD134 Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a second ...

, *

CD137 CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are ''tumor necrosis factor receptor superfamily member 9'' (TNFRSF9), 4-1BB and ''induced by lymphocyte activation'' (ILA). It is of interest to immunolog ...

, *

CD27 CD27 is a member of the tumor necrosis factor receptor superfamily. It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials. Expression During mous ...

, *

CD40 Cluster of differentiation 40, CD40 is a costimulatory protein found on antigen-presenting cells and is required for their activation. The binding of CD154 ( CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of d ...

, * CFLAR, *

CHUK Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the ''CHUK'' gene. IKK-α is part of the IκB kinase ...

, *

Caveolin 1 Caveolin-1 is a protein that in humans is encoded by the ''CAV1'' gene. Function The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits ...

, *

EDARADD Ectodysplasin-A receptor-associated adapter protein is a protein that in humans is encoded by the ''EDARADD'' gene. Function This gene was identified by its association with ectodermal dysplasia, and specifically with hypohidrotic ectodermal d ...

, *

HIVEP3 Transcription factor HIVEP3 is a protein that in humans is encoded by the ''HIVEP3'' gene. Function Members of the ZAS family, such as ZAS3 (HIVEP3), are large proteins that contain a ZAS domain, a modular protein structure consisting of a pai ...

, *

IKK2 IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the ''IKBKB'' (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) gene. Function IKK-β is an enzy ...

, *

Low affinity nerve growth factor receptor The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic facto ...

, *

MAP3K14 Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the ''MAP3K14'' gene. Function This gene encodes mitogen-activated protein kinase kinase kinase 14, NIK, ...

, * MAP3K1, *

MAP3K7IP2 Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the ''MAP3K7IP2'' gene. The protein encoded by this gene is an activator of MAP3K7/ TAK1, which is required for the IL-1 induced act ...

, *

MAP4K2 Mitogen-activated protein kinase kinase kinase kinase 2 is an enzyme that in humans is encoded by the ''MAP4K2'' gene. Function The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is ...

, *

MAP4K5 Mitogen-activated protein kinase kinase kinase kinase 5 is an enzyme that in humans is encoded by the ''MAP4K5'' gene. This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yea ...

, *

RANK Rank is the relative position, value, worth, complexity, power, importance, authority, level, etc. of a person or object within a ranking, such as: Level or position in a hierarchical organization * Academic rank * Diplomatic rank * Hierarchy * ...

, *

RIPK1 Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival ...

, * SPHK1, *

TANK A tank is an armoured fighting vehicle intended as a primary offensive weapon in front-line ground combat. Tank designs are a balance of heavy firepower, strong armour, and good battlefield mobility provided by tracks and a powerful engin ...

, *

TANK-binding kinase 1 TBK1 (TANK-binding kinase 1) is an enzyme with kinase activity. Specifically, it is a serine / threonine protein kinase. It is encoded by the TBK1 gene in humans. This kinase is mainly known for its role in innate immunity antiviral response. Howev ...

, *

TNFAIP3 Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the ''TNFAIP3'' gene. This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded ...

, *

TNFRSF13B Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a protein that in humans is encoded by the TNFRSF13B gene. TNFRSF13B is a transmembrane protein of the TNF re ...

, *

TNFRSF14 Herpesvirus entry mediator (HVEM), also known as tumor necrosis factor receptor superfamily member 14 (TNFRSF14), is a human cell surface receptor of the TNF-receptor superfamily. Nomenclature This protein was originally known as herpesvirus entr ...

, *

TNFRSF1A Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα). Function The protein encoded b ...

, *

TNFRSF1B Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necro ...

, *

TNFSF14 LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3. Nomenclature LIGHT stands for "homolo ...

, *

TRADD Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the ''TRADD'' gene. TRADD is an adaptor protein. Function The protein encoded by this gene is a death domain containing adaptor m ...

, *

TRAF interacting protein TRAF-interacting protein is a protein that in humans is encoded by the ''TRAIP'' gene. This gene encodes a protein that contains an N-terminal RING finger motif and a putative coiled-coil domain. A similar murine protein interacts with TNFR-assoc ...

, *

, and *

UBE2N Ubiquitin-conjugating enzyme E2 N is a protein that in humans is encoded by the ''UBE2N'' gene. Function The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradat ...

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used in the study of TRAF2 function. A conditional

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

line called ''Traf2^{tm1a(EUCOMM)Wtsi}'' was generated at the

Wellcome Trust Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is located on the Wellcome G ...

. Male and female animals underwent a standardized

phenotypic screen In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping

Function

Interactions

Model organisms

References

Further reading