WWC2

Last updated
WWC2
Identifiers
Aliases WWC2 , BOMB, WW and C2 domain containing 2
External IDs MGI: 1261872 HomoloGene: 32618 GeneCards: WWC2
Gene location (Human)
Ideogram human chromosome 4.svg
Chr. Chromosome 4 (human) [1]
Human chromosome 4 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 4q35.1Start183,099,257 bp [1]
End183,320,777 bp [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_024949

NM_133791

RefSeq (protein)

NP_079225

NP_598552

Location (UCSC) Chr 4: 183.1 – 183.32 Mb Chr 8: 47.82 – 47.99 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

WW and C2 domain containing 2 (WWC2) is a protein that in humans is encoded by the WWC2 gene (4q35.1). Though function of WWC2 remains unknown, it has been predicted that WWC2 may play a role in cancer.

Contents

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 [5]


Aliases

A common alias of the gene is BH3-Only Member B (BOMB) [6]

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. [7] WWC3 is located on chromosome X and not much is known about its function.

SequenceGenus/speciesAccession #Seq. lengthSeq. identity
WWC2Homo sapiens NP_079225 1192 aa100%
KIBRA (WWC1)Homo sapiens AA015881 1113 aa49.7%
WWC3Homo sapiens NP_056506 1092 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/A NP_079225 100%
Pan troglodytesChimpanzee6.1 MYA XP_003310624 99%
Heterocephalus glaberNaked mole rat91 MYA EHB18748 88%
Mus musculusMouse91 MYA NP_598552 86%
Orcinus orcaKiller whale97.4 MYA XP_004281794 90%
Bos mutusYak97.4 MYA XP_005903227 84%
Alligator mississippiensisAlligator324.5 MYA XP_006269678 79.2%
Pelodiscus sinensisChinese soft-shelled turtle324.5 MYA XP_006130219 79%
Anas platyrhynchosMallard324.5 MYA EOA93642 78%
Falco peregrinusPeregrine falcon324.5 MYA XP_005230882 77%
Ficedula albicollisCollared flycatcher324.5 MYA XP_005045160 76%
Xenopus (Silurana) tropicalisWestern clawed frog361.2 MYA NP_001004872 71%
Ophiophagus hannahKing cobra362.2 MYA ETE71408 71%
Latimeria chalumnaeCoelacanth430 MYA XP_005989542 72%
Takifugu rubripesPufferfish454.6 MYA XP_003973883 55%
Danio rerioZebrafish454.6 MYA XP_689275 53%
Xiphophorus maculatusSouthern platyfish454.6 MYA XP_005800442 51%
Aplysia californicaCalifornia sea hare (slug)782.7 MYA XP_005096216 51%
Crassostrea gigasPacific oyster910 MYA EKC42771 39%
Anopheles darlingiMosquito910 MYA ETN67979 34%
Drosophila melanogasterFruit fly910 MYA AAF55090.2 28.9%

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. [8] The protein is serine rich with no charge clusters, hydrophobic segments or transmembrane domains. The isoelectric point is 5.23800 [9]

Domains and motifs

WWC2 is a member of the WWC protein family [10] 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. [11] 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. [12]

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 (T) to Cys (C)470
rs191286964C to TArg (R) to Cys (C)1082
rs139606516G to TArg (R) to Leu (L)1082
rs149738870A to GAsn (N) to Ser (S)1084

Interacting proteins

Transcription factors

Transcription factors with highest matrix scores that bind to sequences within the promoter (ID GXP_1499160) 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. [13] One study examined the role of Drosophila KIBRA (WWC1) 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. [14] WWC2 alias, BOMB, was researched in a grant suggesting that BOMB, along with two other genes (APOL6 and APOL1) promoted cell death in p53-null HCT116 cells.

Related Research Articles

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PBDC1 protein-coding gene in the species Homo sapiens

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FAM214A protein-coding gene in the species Homo sapiens

Protein FAM214A, also known as protein family with sequence similarity 214, A (FAM214A) is a protein that, in humans, is encoded by the FAM214A gene. FAM214A is a gene with unknown function found at the q21.2-q21.3 locus on Chromosome 15 (human). The protein product of this gene has two conserved domains, one of unknown function (DUF4210) and another one called Chromosome_Seg. Although the function of the FAM214A protein is uncharacterized, both DUF4210 and Chromosome_Seg have been predicted to play a role in chromosome segregation during meiosis.

Transmembrane protein 134 protein-coding gene in the species Homo sapiens

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FAM63A protein-coding gene in the species Homo sapiens

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C15orf39

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TEDC2 protein-coding gene in the species Homo sapiens

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C1orf94 protein-coding gene in the species Homo sapiens

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TMEM221

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TMEM247 protein-coding gene in the species Homo sapiens

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000151718 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031563 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. AceView. NCBI. WWC2 homo sapiens. https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=WWC2&submit=Go
  6. Gene cards. WWC2. Homo sapiens. https://www.genecards.org/cgi-bin/carddisp.pl?gene=WWC2&search=wwc2
  7. Gene Cards. KIBRA. Homo Sapiens. https://www.genecards.org/cgi-bin/carddisp.pl?gene=WWC1
  8. SDSC Workbench. SAPS Program. WWC2. Homo sapiens
  9. SDSC Workbench. PI Program. WWC2. Homo sapiens
  10. Wennmann DO, Schmitz J, Wehr MC, Krahn MP, Koschmal N, Gromnitza S, Schulze U, Weide T, Chekuri A, Skryabin BV, Gerke V, Pavenstädt H, Duning K, Kremerskothen J (2014). "Evolutionary and molecular facts link the WWC protein family to Hippo signaling". Molecular Biology and Evolution. 31 (7): 1710–23. doi: 10.1093/molbev/msu115 . PMID   24682284.
  11. ExPASy. NetPhos 2.0 Program. http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5341A6B500000A4BB89D0F8C&wait=20
  12. ExPASy. NetPhosK 1.0 Program. http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5341A89700000A4B44994EF8&wait=20
  13. Weissbach A, Siegesmund K, Brüggemann N, Schmidt A, Kasten M, Pichler I, Muhle H, Lohmann E, Lohnau T, Schwinger E, Hagenah J, Stephani U, Pramstaller PP, Klein C, Lohmann K (November 2012). "Exome sequencing in a family with restless legs syndrome". Movement Disorders. 27 (13): 1686–9. doi:10.1002/mds.25191. PMID   23192925. S2CID   11969320.
  14. Katoh M (December 2012). "Function and cancer genomics of FAT family genes (review)". International Journal of Oncology. 41 (6): 1913–8. doi:10.3892/ijo.2012.1669. PMC   3583642 . PMID   23076869.