Heterogeneous nuclear ribonucleoprotein K (also protein K) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''HNRNPK''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
It is found in the
cell nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
that binds to pre-
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
(mRNA) as a component of
heterogeneous ribonucleoprotein particles. The
simian
The simians, anthropoids, or higher primates are an infraorder (Simiiformes ) of primates containing all animals traditionally called monkeys and apes. More precisely, they consist of the parvorders New World monkeys (Platyrrhini) and Cat ...
homolog is known as ''protein H16''. Both proteins bind to single-stranded
DNA as well as to
RNA and can stimulate the activity of
RNA polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of euka ...
, the protein responsible for most
gene transcription
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
. The relative affinities of the proteins for DNA and RNA vary with solution conditions and are inversely correlated, so that conditions promoting strong DNA binding result in weak RNA binding.
RNA binding protein domains in other proteins that are similar to the RNA binding domain of protein K are called K-homology or KH domains.
Protein K has been the subject of study related to
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...
, in which an
RNA editing
RNA editing (also RNA modification) is a molecular process through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after it has been generated by RNA polymerase. It occurs in all living organisms ...
event inducing the
expression
Expression may refer to:
Linguistics
* Expression (linguistics), a word, phrase, or sentence
* Fixed expression, a form of words with a specific meaning
* Idiom, a type of fixed expression
* Metaphorical expression, a particular word, phrase, o ...
of an
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
containing a
point mutation
A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences ...
was found to be specific to cancerous cells.
Function
This gene belongs to the subfamily of ubiquitously expressed
heterogeneous nuclear ribonucleoproteins Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the ...
(hnRNPs). The hnRNPs are
RNA-binding proteins
RNA-binding proteins (often abbreviated as RBPs) are proteins that bind to the double or single stranded RNA in cells and participate in forming ribonucleoprotein complexes.
RBPs contain various structural motifs, such as RNA recognition motif ...
, and they complex with
heterogeneous nuclear RNA
A primary transcript is the single-stranded ribonucleic acid ( RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs ...
(hnRNA). These proteins are associated with
pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm.
The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene is located in the
nucleoplasm
The nucleoplasm, also known as karyoplasm, is the type of protoplasm that makes up the cell nucleus, the most prominent organelle of the eukaryotic cell. It is enclosed by the nuclear envelope, also known as the nuclear membrane. The nucleoplasm ...
and has three repeats of
KH domains
The K Homology (KH) domain is a protein domain that was first identified in the human heterogeneous nuclear ribonucleoprotein (hnRNP) K. An evolutionarily conserved sequence of around 70 amino acids, the KH domain is present in a wide variety o ...
that binds to RNAs. It is distinct among other hnRNP proteins in its binding preference; it binds tenaciously to poly(C). This protein is also thought to have a role during cell cycle progression. Multiple alternatively spliced transcript variants have been described for this gene, but only three variants have been fully described.
Mutations in both copies of ''HNRNPK'' are embryonic lethal in mice. Mice with both copies of the gene knocked out die before the 14th day of
embryonic development
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
.
Clinical significance
Okamoto syndrome
Mutations in ''HNRNPK'' cause
Okamoto syndrome
Okamoto syndrome (OS), also known as Au–Kline syndrome (AKS), is a very rare autosomal dominant genetic condition characterised by congenital hydronephrosis, low muscle tone, heart defects, intellectual disability and characteristic facial f ...
, also known as Au–Kline syndrome.
Blood cancers
Deletions in the region encompassing ''HNRNPK'' have been found in the cells of
acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...
in approximately 2% of cases. Additionally, a majority of mice who have had one of their ''HNRNPK'' genes artificially
knocked out
A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, muay thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...
developed
myeloid cancers, with a third developing
lymphoid cancers and 4% developing
hepatocellular carcinomas
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
It occurs in t ...
. The mice were also smaller, had less developed organs and had higher postnatal mortality (30%). The median lifespan of the mice that survived was less than 50% that of wild-type mice. Deficiencies in HNRNPK appear to specifically reduce the levels of the p42
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
of
CEBPA
CCAAT/enhancer-binding protein alpha is a protein encoded by the ''CEBPA'' gene in humans. CCAAT/enhancer-binding protein alpha is a transcription factor involved in the differentiation of certain blood cells. For details on the CCAAT structural m ...
, which is a
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
involved in the differentiation of certain
blood cells
A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), a ...
, as well as
p21
p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...
(cyclin-dependent kinase inhibitor 1), which is involved in pausing cell development for
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
.
''HNRNPK'' overexpression also appears to contribute to cancers via a different mechanism involving
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
rather than
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
.
Interactions
HNRPK has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
CSK,
*
DDX1,
*
HNRNPL
Heterogeneous nuclear ribonucleoprotein L is a protein that in humans is encoded by the ''HNRNPL'' gene.
Function
Heterogeneous nuclear RNAs (hnRNAs) which include mRNA precursors and mature mRNAs are associated with specific proteins to form ...
,
[
* ]KHDRBS1
KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the ''KHDRBS1'' gene.
This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated ...
,
* PCBP2
Poly(rC)-binding protein 2 is a protein that in humans is encoded by the ''PCBP2'' gene.
Function
The protein encoded by this gene appears to be multifunctional. It along with PCBP-1 and hnRNPK corresponds to the major cellular poly(rC)-binding ...
,
* PRMT1
Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the ''PRMT1'' gene. The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.
Function
...
, and
* PTBP1
Polypyrimidine tract-binding protein 1 is a protein that in humans is encoded by the ''PTBP1'' gene.
This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA-binding protei ...
.[
]
Human proteins containing a KH domain
AKAP1
A kinase anchor protein 1, mitochondrial is an enzyme that in humans is encoded by the ''AKAP1'' gene.
Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that have the common function of binding to the ...
; ANKHD1
Ankyrin repeat and KH domain-containing protein 1 is a protein that in humans is encoded by the ''ANKHD1'' gene.
Function
This gene encodes a protein with multiple ankyrin repeat domains and a single KH domain. Co-transcription of this gene and ...
; ANKRD17
Ankyrin repeat domain-containing protein 17 is a protein that in humans is encoded by the ''ANKRD17'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." mean ...
; ASCC1
Activating signal cointegrator 1 complex subunit 1 (ASCC1) is a protein that in humans is encoded by the ''ASCC1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of here ...
; BICC1; DDX43
Probable ATP-dependent RNA helicase DDX43 is an enzyme that in humans is encoded by the ''DDX43'' gene.
Function
The protein encoded by this gene is an ATP-dependent RNA helicase in the DEAD box
Death is the irreversible cessation of ...
; DDX53
DEAD-box helicase 53 is a protein that in humans is encoded by the DDX53 gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birt ...
; DPPA5;
FMR1
''FMR1'' (Fragile X Messenger Ribonucleoprotein 1) is a human gene that codes for a protein called ''fragile X messenger ribonucleoprotein'', or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development ...
; FUBP1
Far upstream element-binding protein 1 is a protein that in humans is encoded by the ''FUBP1'' gene.
This gene encodes a ssDNA binding protein that activates the far upstream element (FUSE) of c-myc and stimulates expression of c-myc in undiffere ...
; FUBP3; FXR1
Fragile X mental retardation syndrome-related protein 1 is a protein that in humans is encoded by the ''FXR1'' gene.
The protein encoded by this gene is an RNA binding protein that interacts with the functionally similar proteins FMR1 and FXR2. Th ...
; FXR2
Fragile X mental retardation syndrome-related protein 2 is a protein that in humans is encoded by the ''FXR2'' gene.
Function
The protein encoded by this gene is an RNA binding protein containing two KH domains and one RCG box, which is simila ...
; HDLBP
Vigilin is a 110 kDa protein that in humans is encoded by the ''HDLBP'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...
; HNRPK
Heterogeneous nuclear ribonucleoprotein K (also protein K) is a protein that in humans is encoded by the ''HNRNPK'' gene. It is found in the cell nucleus that binds to pre-messenger RNA (mRNA) as a component of heterogeneous ribonucleoprotein par ...
; IGF2BP1
Insulin-like growth factor 2 mRNA-binding protein 1 is a protein that in humans is encoded by the ''IGF2BP1'' gene.
This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four K homo ...
;
IGF2BP2
Insulin-like growth factor 2 mRNA-binding protein 2 is a protein that in humans is encoded by the ''IGF2BP2'' gene.
This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domai ...
; IGF2BP3
Insulin-like growth factor 2 mRNA-binding protein 3 is a protein that in humans is encoded by the ''IGF2BP3'' gene.
The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth f ...
; KHDRBS1
KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the ''KHDRBS1'' gene.
This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated ...
; KHDRBS2; KHDRBS3
KH domain-containing, RNA-binding, signal transduction-associated protein 3 is a protein that in humans is encoded by the ''KHDRBS3'' gene.
Interactions
KHDRBS3 has been shown to interact with SIAH1.
KHDRBS3 interacts with splicing protein Sa ...
; KHSRP; KRR1
KRR1 small subunit processome component homolog is a protein that in humans is encoded by the ''KRR1'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." mean ...
; MEX3A;
MEX3B
RNA-binding protein MEX3B is a protein that in humans is encoded by the ''MEX3B'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...
; MEX3C; MEX3D
Mex-3 homolog D (C. elegans), also known as MEX3D, is a protein that in humans is encoded by the ''MEX3D'' gene.
Function
MEX3D is an RNA binding protein that interacts with AU-rich elements of Bcl-2. Upon binding, MEX3D has a negative regulat ...
; NOVA1
RNA-binding protein Nova-1 is a protein that in humans is encoded by the ''NOVA1'' gene.
This gene encodes a neuron-specific RNA-binding protein, a member of the Nova family of paraneoplastic disease antigens, that is recognized and inhibited by ...
; NOVA2; PCBP1
Poly(rC)-binding protein 1 is a protein that in humans is encoded by the ''PCBP1'' gene.
This intronless gene is thought to have been generated by retrotransposition of a fully processed PCBP-2 mRNA. This gene and PCBP-2 have paralogues (PCBP3 and ...
; PCBP2
Poly(rC)-binding protein 2 is a protein that in humans is encoded by the ''PCBP2'' gene.
Function
The protein encoded by this gene appears to be multifunctional. It along with PCBP-1 and hnRNPK corresponds to the major cellular poly(rC)-binding ...
; PCBP3;
PCBP4; PNO1; PNPT1; QKI
Quaking homolog, KH domain RNA binding (mouse), also known as QKI, is a protein which in humans is encoded by the ''QKI'' gene.
QKI belongs to a family of RNA-binding proteins called STAR proteins for Signal Transduction and Activation of RNA. Th ...
; SF1; TDRKH
Tudor and KH domain-containing protein is a protein that in humans is encoded by the ''TDRKH'' gene.
References
Further reading
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References
Further reading
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External links
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{{PDB Gallery, geneid=3190
RNA-binding proteins