The K Homology (KH) domain is a

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...

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 of nucleic acid-binding proteins. The KH domain binds

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

, and can function in RNA recognition. It is found in multiple copies in several proteins, where they can function cooperatively or independently. For example, in the AU-rich element RNA-binding protein KSRP, which has 4 KH domains, KH domains 3 and 4 behave as independent binding modules to interact with different regions of the AU-rich RNA targets. The solution structure of the first KH domain of FMR1 and of the C-terminal KH domain of hnRNP K determined by nuclear magnetic resonance (NMR) revealed a beta-alpha-alpha-beta-beta-alpha structure. Autoantibodies to

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 ...

, a KH domain protein, cause paraneoplastic opsoclonus ataxia. The KH domain is found at the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

of the ribosomal protein S3. This domain is unusual in that it has a different fold compared to the normal KH domain.

Nucleic acid binding

KH domains bind to either

or single stranded DNA. The nucleic acid is bound in an extended conformation across one side of the domain. The binding occurs in a cleft formed between alpha helix 1, alpha helix 2 the GXXG loop (contains a highly conserved

sequence motif In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''As ...

) and the variable loop. The binding cleft is hydrophobic in nature with a variety of additional protein specific interactions to stabilise the complex. Valverde and colleagues note that, "Nucleic acid base-to-protein aromatic side chain stacking interactions which are prevalent in other types of single stranded nucleic acid binding motifs, are notably absent in KH domain nucleic acid recognition".

Structural groups

Structurally there are two different types of KH domains identified by Grishin which are called type I and type II. The type I domains are mainly found in eukaryotic proteins, while the type II domains are predominantly found in prokaryotes. While both types share a minimal consensus sequence motif they have different structural folds. The type I KH domains have a three stranded beta-sheet where all three strands are anti-parallel. In the type II domain two of the three beta strands are in a parallel orientation. While type I domains are usually found in multiple copies within proteins, the type II are typically found in a single copy per protein.

Human proteins containing this 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 ...

; GLD1;

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 ...

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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 ...

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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 ...

;

; 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 ...

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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 RNA-binding protein PNO1 is a protein that in humans is encoded by the ''PNO1'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or '' ...

; 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

* * * * * * * {{gene-1-stub ...

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References

{{InterPro content, IPR004088 Protein domains