CAPZB

Protein-coding gene in humans
CAPZB
Identifiers
AliasesCAPZB, CAPB, CAPPB, CAPZ, capping actin protein of muscle Z-line beta subunit, capping actin protein of muscle Z-line subunit beta
External IDsOMIM: 601572; MGI: 104652; HomoloGene: 3620; GeneCards: CAPZB; OMA:CAPZB - orthologs
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for CAPZB
Genomic location for CAPZB
Band1p36.13Start19,338,775 bp[1]
End19,485,539 bp[1]
Gene location (Mouse)
Chromosome 4 (mouse)
Chr.Chromosome 4 (mouse)[2]
Chromosome 4 (mouse)
Genomic location for CAPZB
Genomic location for CAPZB
Band4 D3|4 70.59 cMStart138,920,210 bp[2]
End139,019,129 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • muscle layer of sigmoid colon

  • smooth muscle tissue

  • monocyte

  • granulocyte

  • left testis

  • right testis

  • stromal cell of endometrium

  • pylorus

  • popliteal artery

  • tibial arteries
Top expressed in
  • gastrula

  • granulocyte

  • triceps brachii muscle

  • ascending aorta

  • tibiofemoral joint

  • ankle

  • pyloric antrum

  • yolk sac

  • tail of embryo

  • vastus lateralis muscle
More reference expression data
BioGPS




More reference expression data
Gene ontology
Molecular function
  • actin filament binding
  • cadherin binding
  • actin binding
  • protein binding
Cellular component
  • cytoplasm
  • cytosol
  • sarcomere
  • WASH complex
  • extracellular exosome
  • cytoskeleton
  • actin filament
  • actin cytoskeleton
  • F-actin capping protein complex
Biological process
  • regulation of lamellipodium assembly
  • barbed-end actin filament capping
  • regulation of cell morphogenesis
  • blood coagulation
  • cytoskeleton organization
  • actin cytoskeleton organization
  • actin filament capping
  • negative regulation of filopodium assembly
  • endoplasmic reticulum to Golgi vesicle-mediated transport
  • antigen processing and presentation of exogenous peptide antigen via MHC class II
  • cell morphogenesis
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

832

12345

Ensembl

ENSG00000077549

ENSMUSG00000028745

UniProt

P47756

P47757

RefSeq (mRNA)

NM_001313932
NM_001206540
NM_001206541
NM_001282162
NM_004930

NM_001037761
NM_001271405
NM_001271406
NM_009798

RefSeq (protein)

NP_001193469
NP_001193470
NP_001269091
NP_001300861
NP_004921

NP_001032850
NP_001258334
NP_033928

Location (UCSC)Chr 1: 19.34 – 19.49 MbChr 4: 138.92 – 139.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

F-actin-capping protein subunit beta, also known as CapZβ, is a protein that in humans is encoded by the CAPZB gene.[5] CapZβ functions to cap actin filaments at barbed ends in muscle and other tissues.

Structure

CapZβ can exist as 3 unique β subunits, dependent on alternative splicing mechanisms.[6][7][8][9] CapZβ1 is 31.4 kDa and 277 amino acids in length, CapZβ2 is 30.6 kDa and 272 amino acids in length, and CapZβ3 is 301 amino acids in length (N-terminal extension of 29 amino acids relative to the β2 subunit.[7]). In contrast, the 3 α subunits arise from distinct genes.[10] CapZ is a heterodimer composed of an α and β subunit. In muscle, capping protein α1 subunit and β1 subunit are localized at the Z-disc, and form CapZ.[11] CapZ interacts with α-actinin, nebulette, nebulin, HSC70.[12] at the Z-disc.

Function

CAPZB is a member of the F-actin capping protein family. This gene encodes the beta subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.[5]

CapZβ functions to cap actin filaments at barbed (+) ends, thus controlling the rate of G-actin polymerization to F-actin and corresponding filament length. CapZ works in concert with tropomodulin, which caps actin at pointed ends. In muscle, the interaction of CapZ with actin is critical during myofibrilogenesis, as administration of a CapZ monoclonal antibody or expression of CapZ mutant protein disrupts actin filament formation and assembly of myofibrils.[13] Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors actin at Z-discs and CapZβ2 at intercalated discs.[14][15] Overexpression of CapZβ2 (and concomitant down-regulation of CapZβ1) in mice resulted in a diseased phenotype with stunted growth, irregular gait, labored breathing and juvenile lethality. Ultrastructural measurements showed severely disrupted myofibrillar architecture.[15] A function of CapZβ in transducing protein kinase C signaling in cardiac myocytes was illuminated by a study in skinned cardiac fibers which demonstrated that partial, transgenic reduction of CapZβ attenuated the functional effect of protein kinase C on contraction and disturbed normal PKC isoform translocation patterns following phenylephrine or endothelin-1 treatment.[16] A later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to myofilaments.[17] Regarding the turnover of CapZβ, it was recently demonstrated that the protein turnover of CapZβ1 is in part regulated by the Bcl-2–associated athanogene, BAG3, through a mechanism involving the association between HSC70 and CapZβ1.[12]

Clinical Significance

There is currently little to no data available on the relationship between the CAPZB gene and human disease.

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000077549 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028745 – 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. ^ a b "Entrez Gene: CAPZB capping protein (actin filament) muscle Z-line, beta".
  6. ^ Schafer DA, Korshunova YO, Schroer TA, Cooper JA (October 1994). "Differential localization and sequence analysis of capping protein beta-subunit isoforms of vertebrates". The Journal of Cell Biology. 127 (2): 453–65. doi:10.1083/jcb.127.2.453. PMC 2120197. PMID 7929588.
  7. ^ a b von Bülow M, Rackwitz HR, Zimbelmann R, Franke WW (May 1997). "CP beta3, a novel isoform of an actin-binding protein, is a component of the cytoskeletal calyx of the mammalian sperm head". Experimental Cell Research. 233 (1): 216–24. doi:10.1006/excr.1997.3564. PMID 9184090.
  8. ^ "F-actin-capping protein subunit beta". COPaKB.
  9. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  10. ^ Hart MC, Korshunova YO, Cooper JA (1997). "Vertebrates have conserved capping protein alpha isoforms with specific expression patterns". Cell Motility and the Cytoskeleton. 38 (2): 120–32. doi:10.1002/(SICI)1097-0169(1997)38:2<120::AID-CM2>3.0.CO;2-B. PMID 9331217.
  11. ^ Casella JF, Craig SW, Maack DJ, Brown AE (July 1987). "Cap Z(36/32), a barbed end actin-capping protein, is a component of the Z-line of skeletal muscle". The Journal of Cell Biology. 105 (1): 371–9. doi:10.1083/jcb.105.1.371. PMC 2114938. PMID 3301868.
  12. ^ a b Hishiya A, Kitazawa T, Takayama S (November 2010). "BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress". Circulation Research. 107 (10): 1220–31. doi:10.1161/CIRCRESAHA.110.225649. PMC 2980587. PMID 20884878.
  13. ^ Schafer DA, Hug C, Cooper JA (January 1995). "Inhibition of CapZ during myofibrillogenesis alters assembly of actin filaments". The Journal of Cell Biology. 128 (1–2): 61–70. doi:10.1083/jcb.128.1.61. PMC 2120327. PMID 7822423.
  14. ^ Papa I, Astier C, Kwiatek O, Raynaud F, Bonnal C, Lebart MC, Roustan C, Benyamin Y (February 1999). "Alpha actinin-CapZ, an anchoring complex for thin filaments in Z-line". Journal of Muscle Research and Cell Motility. 20 (2): 187–97. doi:10.1023/A:1005489319058. PMID 10412090. S2CID 25681698.
  15. ^ a b Hart MC, Cooper JA (December 1999). "Vertebrate isoforms of actin capping protein beta have distinct functions In vivo". The Journal of Cell Biology. 147 (6): 1287–98. doi:10.1083/jcb.147.6.1287. PMC 2168092. PMID 10601341.
  16. ^ Pyle WG, Hart MC, Cooper JA, Sumandea MP, de Tombe PP, Solaro RJ (June 2002). "Actin capping protein: an essential element in protein kinase signaling to the myofilaments". Circulation Research. 90 (12): 1299–306. doi:10.1161/01.res.0000024389.03152.22. PMID 12089068.
  17. ^ Yang FH, Pyle WG (March 2012). "Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning". Journal of Molecular and Cellular Cardiology. 52 (3): 761–72. doi:10.1016/j.yjmcc.2011.11.013. PMID 22155006.

Further reading

  • Barron-Casella EA, Torres MA, Scherer SW, Heng HH, Tsui LC, Casella JF (September 1995). "Sequence analysis and chromosomal localization of human Cap Z. Conserved residues within the actin-binding domain may link Cap Z to gelsolin/severin and profilin protein families". The Journal of Biological Chemistry. 270 (37): 21472–9. doi:10.1074/jbc.270.37.21472. PMID 7665558.
  • Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
  • Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.
  • Bruneel A, Labas V, Mailloux A, Sharma S, Royer N, Vinh J, Pernet P, Vaubourdolle M, Baudin B (October 2005). "Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis". Proteomics. 5 (15): 3876–84. doi:10.1002/pmic.200401239. PMID 16130169. S2CID 26007149.
  • Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
  • Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, Colwill K, Starostine A, Metalnikov P, Pawson T (May 2006). "A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells". Cell. 125 (3): 535–48. doi:10.1016/j.cell.2006.02.045. PMID 16678097. S2CID 18651810.
  • Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  • Mass spectrometry characterization of human CAPZB at COPaKB
  • Human CAPZB genome location and CAPZB gene details page in the UCSC Genome Browser.
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  • 1izn: Crystal Structure of Actin Filament Capping Protein CapZ
    1izn: Crystal Structure of Actin Filament Capping Protein CapZ