WWC2

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.

WWC2
Identifiers
AliasesWWC2, BOMB, WW and C2 domain containing 2
External IDsMGI: 1261872 HomoloGene: 32618 GeneCards: WWC2
Gene location (Human)
Chr.Chromosome 4 (human)[1]
Band4q35.1Start183,099,257 bp[1]
End183,320,777 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

80014

52357

Ensembl

ENSG00000151718

ENSMUSG00000031563

UniProt

Q6AWC2

Q6NXJ0

RefSeq (mRNA)

NM_024949

NM_133791

RefSeq (protein)

NP_079225

NP_598552

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

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 sapiensNP_0792251192 aa100%
KIBRA (WWC1)Homo sapiensAA0158811113 aa49.7%
WWC3Homo sapiensNP_0565061092 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/ANP_079225100%
Pan troglodytesChimpanzee6.1 MYAXP_00331062499%
Heterocephalus glaberNaked mole rat91 MYAEHB1874888%
Mus musculusMouse91 MYANP_59855286%
Orcinus orcaKiller whale97.4 MYAXP_00428179490%
Bos mutusYak97.4 MYAXP_00590322784%
Alligator mississippiensisAlligator324.5 MYAXP_00626967879.2%
Pelodiscus sinensisChinese soft-shelled turtle324.5 MYAXP_00613021979%
Anas platyrhynchosMallard324.5 MYAEOA9364278%
Falco peregrinusPeregrine falcon324.5 MYAXP_00523088277%
Ficedula albicollisCollared flycatcher324.5 MYAXP_00504516076%
Xenopus (Silurana) tropicalisWestern clawed frog361.2 MYANP_00100487271%
Ophiophagus hannahKing cobra362.2 MYAETE7140871%
Latimeria chalumnaeCoelacanth430 MYAXP_00598954272%
Takifugu rubripesPufferfish454.6 MYAXP_00397388355%
Danio rerioZebrafish454.6 MYAXP_68927553%
Xiphophorus maculatusSouthern platyfish454.6 MYAXP_00580044251%
Aplysia californicaCalifornia sea hare (slug)782.7 MYAXP_00509621651%
Crassostrea gigasPacific oyster910 MYAEKC4277139%
Anopheles darlingiMosquito910 MYAETN6797934%
Drosophila melanogasterFruit fly910 MYAAAF55090.228.9%

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:

  • STAT (signal transducer and activator of transcription)
  • Muscle TATA box
  • NOLF (neuron-specific olfactory factor)
  • XCPE (X gene core promoter element 1)
  • CTCF (CCCTC-binding factor)
  • HDBP (Huntington's disease gene regulatory region)
  • OCT1 (octamer binding protein)
  • E2FF (E2F-myc activator cell cycle regulator)
  • ZF57 (KRAB domain zinc finger protein 57)
  • ZF07 (C2H2 zinc finger transcription factor 7)
  • EGRF (EGR/nerve growth factor induced protein)
  • CDEF (cell cycle dependent element - CDF-1 binding site)
  • AP2F (activator protein 2)

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.

References

  1. GRCh38: Ensembl release 89: ENSG00000151718 - Ensembl, May 2017
  2. 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.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.