ZC3H12B

ZC3H12B, also known as CXorf32 or MCPIP2, is a protein encoded by gene ZC3H12B located on chromosome Xq12 in humans.

ZC3H12B
Identifiers
Aliases	ZC3H12B, CXorf32, MCPIP2, zinc finger CCCH-type containing 12B
External IDs	OMIM: 300889; MGI: 2442133; HomoloGene: 19395; GeneCards: ZC3H12B; OMA:ZC3H12B - orthologs
Gene location (Human) Chr. X chromosome (human) Band Xq11.2-q12 Start 65,366,638 bp End 65,507,887 bp
Gene location (Mouse) Chr. X chromosome (mouse) Band X|X C3 Start 94,755,284 bp End 94,976,243 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in prefrontal cortex gonad Brodmann area 23 superior frontal gyrus primary visual cortex postcentral gyrus dorsolateral prefrontal cortex middle temporal gyrus entorhinal cortex Achilles tendon Top expressed in dentate gyrus of hippocampal formation granule cell hippocampus proper primary visual cortex Cortex of frontal lobe cerebellar cortex superior frontal gyrus genital tubercle zygote tail of embryo primary oocyte More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 340554 547176 Ensembl ENSG00000102053 ENSMUSG00000035045 UniProt Q5HYM0 n/a RefSeq (mRNA) NM_001010888 NM_001034907 RefSeq (protein) NP_001010888 n/a Location (UCSC) Chr X: 65.37 – 65.51 Mb Chr X: 94.76 – 94.98 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Gene

The ZC3H12B gene is composed of 19,709 base pairs (bp) and contains 5 exons. It is located on the X chromosome at q12 on the plus strand.

ZC3H12B contains a ribonuclease domain, as well as a CCCH-type zinc finger domain. Ribonucleases (RNases) degrade RNA and are involved in the RNA maturation process. They are also a line of defense against viral RNA (D'Alessio and Riordan 1997). CCCH-type zinc fingers are associated with mRNA destabilization. Interestingly, CCCH-type zinc fingers have been shown to turn over mRNA without the removal of the PolyA tail (Lai and Blackshear 2001). ZC3H12B and its paralogs ZC3H12A, ZC3H12C and ZC3H12D all contain CCCH-type zinc finger domains, which have been associated with cell cycle and growth phase transitions in eukaryotes (InterPro).

Promoter

Genomatix ElDorado program predicted a 601 bp promoter upstream of the ZC3H12B gene with multiple transcription factor binding sites including nuclear factor of activated T-cells and ribonucleoprotein associated zinc finger protein MOK-2 (also known as ZNF239).

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  Conceptual Translation of ZC3H12B annotated with predicted phosphorylation sites, 0-B-GlcNAc sites, exon boundaries, secondary structures and conserved regions.
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  ZC3H12B Locus.
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  Transcription factor binding sites in the promoter of ZC3H12B.

mRNA

ZC3H12B contains 7273 bp mRNA. There is only one predicted transcript by Aceview. discussion of folding patterns, discussion of introns and exons INSERT ACEVIEW PICTURE

Protein

ZC3H12B is a probable ribonuclease containing CCCH-type Zinc finger domain and ribonuclease domains. The 836 amino acid protein has a predicted molecular weight of 94.2 kdal. It does not contain a signal peptide or a transmembrane region. PSORTII predicted 65.2% probability of nuclear location. CCCH-type zinc fingers and ribonucleases are presumabely located in the nucleus for RNA cleaving and specifically, RNA hairpin cleaving (Boysen and Hearn 2008).

Structural characteristics

(ie. unmodified) and topology - MAP The protein secondary structure is a mixture of alpha helices and beta strands. The two domains identified so far are the ribonuclease and CCCH-type zinc finger domains.

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  Cn3D rendering of Mcpip1 conserved domain with zinc-finger motif.

Post-translational Modification

NetPhos 2.0. predicted 63 phosphorylation sites in ZC3H12B, which are marked on the conceptual translation. YinOYang1.2. predicted three 0-Beta-GlcNAc attachment sites, which are competing with phosphorylation sites. 0-Beta-GlcNAc is presumably the only type of glycosylation occurring in the nucleus and/or cytoplasm of cells. There is a notable link between antigen activation by lymphocytes and dynamic 0-B-Glycosylation in nuclear proteins (Hart and Akimoto). There were no predicted acetylation sites at the N-terminus of the protein. This is interesting because approximately 85% of human proteins are acetylated at the N terminus for synthesis, stabilization and localization of proteins (Van Damm et al).

Evolution

Select domains of ZC3H12B are conserved in most vertebrates, arthropods and annelids. There are not conserved domains in domains bacteria or archaea. There were not significantly conserved domains in yeasts, plants or protists.

Paralogs

Name	Species	NCBI Accession Number	Length (AA)	Protein Identity
ZC3H12B	Homo sapiens	NM_001010888.3	836aa	100%
ZC3H12A	Homo sapiens	NM_025079.2	599aa	68%
ZC3H12C	Homo sapiens	NM_033390.1	883aa	53%
ZC3H12D	Homo sapiens	NM_207360.2	527aa	61%

Orthologs

Species	Species common name	Divergence (MYA)	NCBI Accession Number (Protein)	Length (amino acids)	Protein Identity	Similarity	Notes
Homo sapiens	Human	n/a	NP_001010888.3	836aa	100%	100%
Pan paniscus	Chimpanzee	6.3	XP_003816967.1	836aa	99%	99%
Pongo abelii	Orangutan	15.7	XP_002831786.1	836aa	99%	99%
Macaca mulatta	Rhesus Monkey	29	XP_002806307.1	836aa	99%	99%
Callithrix jacchus	Marmoset	42.6	XP_002762992.2	836aa	98%	98%
Mus musculus	Mouse	92.3	NP_001030079.2	835aa	91%	94%
Sus scrofa	Pig	94.2	XP_003360389.1	836aa	93%	96%
Gallus gallus	Chicken	296	XP_003641177.1	837aa	77%	85%
Chrysemys picta bellii	Painted Turtle	296	XP_005279572.1	838aa	78%	86%
Oryzias latipes	Medaka	400.1	XP_004076599.1	845aa	67%	77%
Gadus morhua	Atlantic Cod	400.1	AFK76491.1	842aa	29%	44%
Danio rerio	Zebra Fish	400.1	XP_001342172.3	982aa	68%	77%
Petromyzon marinus	Lamprey	535.7	ABO21295.1	222aa	44%	58%
Branchiostoma floridae	Lancelet	713.2	XP_002598834.1	492aa	66%	79%
Ciona intestinalis	Vase Tunicate	722.5	XP_002125834.1	863aa	54%	66%
Strongylocentrotus purpuratus	Purple Sea Urchin	742.9	XP_787030.3	974aa	58%	72%
Aplysiomorpha californica	Sea Hare	782.7	XP_005113312.1	1269aa	51%	69%
Drosophila grimshawi	Hawaii Fruit Fly	782.7	XP_001994140.1	548aa	51%	69%
Anopheles gambiae	Mosquito	782.7	XP_321880	637aa	59%	75%
Apis mellifera	Honey Bee	782.7	XP_397264	652aa	58%	73%
Caenorhabditis elegans	Round Worm (Nematode)	937.5	NP_491985.4	634aa	46%	64%

Expression and Function

Microarrays in normal tissue expression profiling showed increased expression of the gene in the pancreas, prostate, brain, spinal cord and thymus (GEO). Unlike its paralogs, it is not expressed in macrophage-activated tissues, which indicates the paralogous relationship to the inflammatory response (Liang et al 2008).

ZC3H12B is expressed transiently in brain, thymus and testis tissues (EST)

Interaction

Predicted interactions by Ingenuity Systems showed no drug targeting molecules in pathway and no known drug targets. The listed top functions and diseases were cancer, organismal injury and abnormalities, reproductive system disease. Several miRNA interactions were predicted.

Clinical significance

Deletions of the Xq12 locus has resulted in several disorders such as androgen insensitivity, susceptibility to prostate cancer, spinal and bulbar muscular atrophy of Kennedy and mental retardation; however, no link has been found between these diseases and ZC3H12B.

References

Liang J, Song W, Tromp G, Kolattukudy PE, Fu M. 2008. Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation. Journal of Biological Chemistry. 283(10):6337-46.

Boysen, R.I. and Hearn, M.T.W. 2008. The metal binding properties of the CCCH motif of the 50S ribosomal protein L36 from Thermus thermophilus.

Hart, G.W. and Akimoto, Y. The O-GlcNAc Modification. Essentials of Glycobiology. 2nd edition.

Van Damme, Petra; Hole, Kristine; Pimenta-Marques, Ana; Helsens, Kenny; Vandekerckhove, Joël; Martinho, Rui G.; Gevaert, Kris; Arnesen, Thomas; Snyder, Michael (7 July 2011). "NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation". PLoS Genetics 7 (7): e1002169.

Ribonuclease activity is a common property of Arabidopsis CCCH-containing zinc-finger proteins.

InterPro. http://www.ebi.ac.uk/interpro/entry/IPR000571

External Links

1 NCBI (National Center for Biotechnology Information) [www.ncbi.nlm.nih.gov]

2 HGNC (HUGO Gene Nomenclature Comittee) [www.genenames.org]

3 GC (Gene Cards) [www.genecards.org]

4 OMIM (Online Mendelian Inheritance in Man)[1]

5 Ensembl (Ensembl)[www.ensembl.org]

6 GS (Google Scholar) [www.scholar.google.com]

7 UniProtKB/Swissprot (UniProtein Knowlegdebase/Swissprot) [www.uniprot.org]