WWC2


WW and C2 domain containing 2 is a protein that in humans is encoded by the WWC2 gene. Though function of WWC2 remains unknown, it has been predicted that WWC2 may play a role in cancer.

Gene

Locus
The human gene WWC2 is found on chromosome 4 at band 4q35.1. The gene is found on the plus strand of the chromosome and is 8,822 base pairs long. The gene contains 23 exons. The WWC2 locus is quite complex and appears to produce several proteins with no sequence overlap
Aliases
A common alias of the gene is BH3-Only Member B

Homology

Paralogs
There are two paralogs of WWC2 found in humans, WWC1 and WWC3. WWC1 is located on chromosome 5 and is a probable regulator of the Hippo signaling pathway that plays a role in tumor suppression by restricting proliferation and promoting apoptosis. WWC3 is located on chromosome X and not much is known about its function.
SequenceGenus/speciesAccession #Seq. lengthSeq. identity
WWC2Homo sapiens1192 aa100%
KIBRA Homo sapiens1113 aa49.7%
WWC3Homo sapiens1092 aa41.2%

Orthologs
WWC2 is highly conserved in Mammalia, Aves, Reptilia, and Amphibia, as well as the rare coelacanth, which is more closely related to lungfish, reptiles, and mammals than ray finned fish. WWC2 is conserved in some Actinopterygii, Gastropoda, and Bivalvia. However, WWC2 is not well conserved in Insecta.
Genus/SpeciesCommon nameDate of divergenceAccession #Seq. identity
Homo sapiensHumanN/A100%
Pan troglodytesChimpanzee6.1 MYA99%
Heterocephalus glaberNaked mole rat91 MYA88%
Mus musculusMouse91 MYA86%
Orcinus orcaKiller whale97.4 MYA90%
Bos mutusYak97.4 MYA84%
Alligator mississippiensisAlligator324.5 MYA79.2%
Pelodiscus sinensisChinese soft-shelled turtle324.5 MYA79%
Anas platyrhynchosMallard324.5 MYA78%
Falco peregrinusPeregrine falcon324.5 MYA77%
Ficedula albicollisCollared flycatcher324.5 MYA76%
Xenopus tropicalisWestern clawed frog361.2 MYA71%
Ophiophagus hannahKing cobra362.2 MYA71%
Latimeria chalumnaeCoelacanth430 MYA72%
Takifugu rubripesPufferfish454.6 MYA55%
Danio rerioZebrafish454.6 MYA53%
Xiphophorus maculatusSouthern platyfish454.6 MYA51%
Aplysia californicaCalifornia sea hare 782.7 MYA51%
Crassostrea gigasPacific oyster910 MYA39%
Anopheles darlingiMosquito910 MYA34%
Drosophila melanogasterFruit fly910 MYA28.9%

Protein

Primary sequence
The gene encodes a protein also called WWC2 which is 1,192 amino acids long. The molecular weight of the protein is 133.9 kilodaltons. The protein is serine rich with no charge clusters, hydrophobic segments or transmembrane domains. The isoelectric point is 5.23800
Domains and motifs
WWC2 is a member of the WWC protein family which consists of a WW domain and a C2 domain.
WWC2 contains two WW domains and one C2 domain. WWC2 also contains two domains of unknown function, DUF342 and DUF444. A leucine zipper is located at position 854.
Post translational modifications
The WWC2 protein is predicted to be highly phosphorylated. There are 89 predicted sites of serine phosphorylation, 17 predicted sites of threonine phosphorylation, and 11 predicted sites of tyrosine phosphorylation. These numbers were relatively consistent in orthologous proteins.
It is also predicted that p38 mitogen-activated protein kinases and glycogen synthase kinase 3 bind at position T3, and casein kinase 2 binds at positions S13 and T50.

Expression

Expression
WWC2 is expressed at a low level, and is tissue specific to the uterus, thyroid, lung, and liver. WWC2 expression is found to be elevated in the blastocyst and fetal stages of development.
Transcript variants
Many transcript variants exist for WWC2. Those that change a highly conserved amino acid residue, or surround a highly conserved amino acid residue are listed below:
SNPAlleleProtein residueAmino acid position
rs200024780A to GTyr to Cys 470
rs191286964C to TArg to Cys 1082
rs139606516G to TArg to Leu 1082
rs149738870A to GAsn to Ser 1084

Interacting proteins

Transcription factors
Transcription factors with highest matrix scores that bind to sequences within the promoter are shown below:
Proteins
Potential interacting proteins include: YWHAZ, YWHAQ, RUVBL1, and REPS1.

Clinical significance and Current bioinformation

While the exact function of WWC2 remains unknown, several mutations and variants of WWC2 have been researched in disease. A novel missense mutation in WWC2 was analyzed in Restless Leg Syndrome, but was not identified as a candidate gene. One study examined the role of Drosophila KIBRA in the Expanded-Hippo-Warts signaling cascade, which is involved with tumor suppression. The study stated that copy number aberration, translocation, and point mutations of WWC2, as well as other genes, should be further investigated in human cancers. WWC2 alias, BOMB, was researched in a grant suggesting that BOMB, along with two other genes promoted cell death in p53-null HCT116 cells.