The K Homology domain is a protein domain

Protein domain

A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

 that was first identified in the human heterogeneous nuclear ribonucleoprotein (hnRNP) K

Protein K (gene expression)

Protein K is a human protein found in the cell nucleus that binds to pre-messenger RNA as a component of heterogeneous ribonucleoprotein particles. The simian 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...

. 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

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

, 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

NOVA1

RNA-binding protein Nova-1 is a protein that in humans is encoded by the NOVA1 gene.-Further reading:...

, a KH domain protein, cause paraneoplastic opsoclonus ataxia. The KH domain is found at the N-terminus 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 RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 or single stranded DNA. The nucleic acid is bound in en 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

Sequence motif

In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance...

) 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 predominatly 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

AKAP1

A kinase anchor protein 1, mitochondrial is an enzyme that in humans is encoded by the AKAP1 gene.-Interactions:AKAP1 has been shown to interact with MYCBP, C3orf15, PRKAR1A, PRKAR2A and PRKAR1B.-Further reading:...

; ANKHD1

ANKHD1

Ankyrin repeat and KH domain-containing protein 1 is a protein that in humans is encoded by the ANKHD1 gene.-Further reading:...

; ANKRD17

ANKRD17

Ankyrin repeat domain-containing protein 17 is a protein that in humans is encoded by the ANKRD17 gene.-Further reading:...

; ASCC1; BICC1; DDX43

DDX43

Probable ATP-dependent RNA helicase DDX43 is an enzyme that in humans is encoded by the DDX43 gene.-Further reading:...

; DDX53; DPPA5;
FMR1

FMR1

FMR1 is a human gene that codes for a protein called fragile X mental retardation protein, or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function...

; FUBP1; FUBP3; FXR1

FXR1

Fragile X mental retardation syndrome-related protein 1 is a protein that in humans is encoded by the FXR1 gene.-Interactions:FXR1 has been shown to interact with FXR2 and FMR1.-Further reading:...

; FXR2

FXR2

Fragile X mental retardation syndrome-related protein 2 is a protein that in humans is encoded by the FXR2 gene.-Interactions:FXR2 has been shown to interact with FXR1, LCMT1, FMR1 and CYFIP1.-Further reading:...

; GLD1; HDLBP

HDLBP

Vigilin is a protein that in humans is encoded by the HDLBP gene.-Further reading:...

; HNRPK

HNRPK

Heterogeneous nuclear ribonucleoprotein K is a protein that in humans is encoded by the HNRNPK gene.-Interactions:HNRPK has been shown to interact with KHDRBS1, PCBP2, PTBP1, DDX1, PRMT1, HNRNPL and C-src tyrosine kinase.-Further reading:...

; IGF2BP1

IGF2BP1

Insulin-like growth factor 2 mRNA-binding protein 1 is a protein that in humans is encoded by the IGF2BP1 gene.-Further reading:...

;
IGF2BP2

IGF2BP2

Insulin-like growth factor 2 mRNA-binding protein 2 is a protein that in humans is encoded by the IGF2BP2 gene.-Further reading:...

; IGF2BP3

IGF2BP3

Insulin-like growth factor 2 mRNA-binding protein 3 is a protein that in humans is encoded by the IGF2BP3 gene.-Further reading:...

; KHDRBS1

KHDRBS1

KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the KHDRBS1 gene.-Further reading:...

; KHDRBS2; KHDRBS3

KHDRBS3

KH domain-containing, RNA-binding, signal transduction-associated protein 3 is a protein that in humans is encoded by the KHDRBS3 gene.-Further reading:...

; KHSRP

KHSRP

Far upstream element-binding protein 2 is a protein that in humans is encoded by the KHSRP gene.-Further reading:...

; KRR1

KRR1

KRR1 small subunit processome component homolog is a protein that in humans is encoded by the KRR1 gene.-Further reading:...

; MEX3A;
MEX3B

MEX3B

RNA-binding protein MEX3B is a protein that in humans is encoded by the MEX3B gene.-Further reading:...

; MEX3C; MEX3D

MEX3D

Mex-3 homolog D , 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...

; NOVA1

NOVA1

RNA-binding protein Nova-1 is a protein that in humans is encoded by the NOVA1 gene.-Further reading:...

; NOVA2; PCBP1

PCBP1

Poly-binding protein 1 is a protein that in humans is encoded by the PCBP1 gene.-Further reading:...

; PCBP2

PCBP2

Poly-binding protein 2 is a protein that in humans is encoded by the PCBP2 gene.In humans, the PCBP2 gene overlaps with TUC338, a transcribed ultra-conserved element implicated in Hepatocellular carcinoma.-Interactions:...

; PCBP3

PCBP3

Poly-binding protein 3 is a protein that in humans is encoded by the PCBP3 gene.-Further reading:...

;
PCBP4

PCBP4

Poly-binding protein 4 is a protein that in humans is encoded by the PCBP4 gene.-Further reading:...

; PNO1

PNO1

RNA-binding protein PNO1 is a protein that in humans is encoded by the PNO1 gene.-Further reading:...

; PNPT1; QKI

QKI

Quaking homolog, KH domain RNA binding , 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. They have an HNRNPK homology domain embedded in a 200-amino acid...

; SF1

SF1 (gene)

Splicing factor 1 also known as zinc finger protein 162 is a protein that in humans is encoded by the SF1 gene.Splicing factor SF1 is involved in the ATP-dependent formation of the spliceosome complex.-Interactions:...

; TDRKH

TDRKH

Tudor and KH domain-containing protein is a protein that in humans is encoded by the TDRKH gene.-Further reading:...

;