KH domain

KH domain
KH domain
Identifiers
Symbol	KH_2
Pfam	PF07650
InterPro	IPR004044
SMART	KH
PROSITE	PS50823
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1ega , 1fjg , 1gix , 1hnw , 1hnx , 1hnz , 1hr0 , 1i94 , 1i95 , 1i96 , 1i97 , 1ibk , 1ibl , 1ibm , 1j5e , 1n32 , 1n33 , 1n34 , 1n36 , 1vs5 , 1vs7 , 1wf3 , 1wh9 , 1xmo , 1xmq , 1xnq , 1xnr , 1yl4 , 2avy , 2aw7 , 2b64 , 2b9m , 2b9o , 2e5l , 2f4v , 2hgi , 2hgp , 2hgr , 2hhh , 2i2p , 2i2u , 2j00 , 2j02 , 2ow8 , 2qal , 2qan , 2qb9 , 2qbb , 2qbd , 2qbf , 2qbh , 2qbj , 2qnh , 2qou , 2qow , 2qoy , 2qp0 , 2uu9 , 2uua , 2uub , 2uuc , 2uxb , 2uxc , 2uxd , 2v46 , 2v48 , 2vho , 2vhp , 2vqe , 2vqf , 2z4k , 2z4m , 3d5a , 3d5c , 3df1 , 3df3 , 3f1e , 3f1g

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1dt4 , 1dtj , 1e3h , 1e3p , 1ec6 , 1j4w , 1j5k , 1k1g , 1khm , 1tua , 1vig , 1vih , 1we8 , 1wvn , 1x4m , 1x4n , 1ztg , 1zzi , 1zzj , 1zzk , 2axy , 2ba0 , 2bl5 , 2cpq , 2cte , 2ctf , 2ctj , 2ctk , 2ctl , 2ctm , 2fmr , 2je6 , 2jea , 2p2r , 2pqu , 2py9 , 2z0s

KH domain
KH domain
	Structure of a KH domain from the human protein vigilin.
Identifiers
Symbol	KH_1
Pfam	PF00013
Pfam clan	CL0007
InterPro	IPR018111
SMART	KH
SCOP2	1vig / SCOPe / SUPFAM
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1dt4 , 1dtj , 1e3h , 1e3p , 1ec6 , 1j4w , 1j5k , 1k1g , 1khm , 1tua , 1vig , 1vih , 1we8 , 1wvn , 1x4m , 1x4n , 1ztg , 1zzi , 1zzj , 1zzk , 2axy , 2ba0 , 2bl5 , 2cpq , 2cte , 2ctf , 2ctj , 2ctk , 2ctl , 2ctm , 2fmr , 2je6 , 2jea , 2p2r , 2pqu , 2py9 , 2z0s

Last updated April 08, 2024

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 of nucleic acid-binding proteins. The KH domain binds RNA, and can function in RNA recognition.^[1] 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.^[1] 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.^[2]^[3] Autoantibodies to NOVA1, 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.^[4]

Nucleic acid binding

KH domains bind to either RNA 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) and the variable loop.^[5] 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".^[5]

Structural groups

Structurally there are two different types of KH domains identified by Grishin which are called type I and type II.^[4] 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.^[5]

Human proteins containing this domain

AKAP1; ANKHD1; ANKRD17; ASCC1; BICC1; DDX43; DDX53; DPPA5; FMR1; FUBP1; FUBP3; FXR1; FXR2; GLD1; HDLBP; HNRPK; IGF2BP1; IGF2BP2; IGF2BP3; KHDRBS1; KHDRBS2; KHDRBS3; KHSRP; KRR1; MEX3A; MEX3B; MEX3C; MEX3D; NOVA1; NOVA2; PCBP1; PCBP2; PCBP3; PCBP4; PNO1; PNPT1; QKI; SF1; TDRKH;

Related Research Articles

Nucleoproteins are proteins conjugated with nucleic acids. Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.

<span class="mw-page-title-main">Heterogeneous ribonucleoprotein particle</span>

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 proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm. Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation.

In molecular biology, LSm proteins are a family of RNA-binding proteins found in virtually every cellular organism. LSm is a contraction of 'like Sm', because the first identified members of the LSm protein family were the Sm proteins. LSm proteins are defined by a characteristic three-dimensional structure and their assembly into rings of six or seven individual LSm protein molecules, and play a large number of various roles in mRNA processing and regulation.

rRNA 2'-O-methyltransferase fibrillarin is an enzyme that in humans is encoded by the FBL gene.

Heterogeneous nuclear ribonucleoprotein A1 is a protein that in humans is encoded by the HNRNPA1 gene. Mutations in hnRNP A1 are causative of amyotrophic lateral sclerosis and the syndrome multisystem proteinopathy.

Heterogeneous nuclear ribonucleoprotein 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 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 polymerase II, the protein responsible for most gene transcription. 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.

Heterogeneous nuclear ribonucleoproteins A2/B1 is a protein that in humans is encoded by the HNRNPA2B1 gene.

snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein that in humans is encoded by the SNRNP70 gene. snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease. U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.

Heterogeneous nuclear ribonucleoprotein U is a protein that in humans is encoded by the HNRNPU gene.

Poly(rC)-binding protein 1 is a protein that in humans is encoded by the PCBP1 gene.

Poly(rC)-binding protein 2 is a protein that in humans is encoded by the PCBP2 gene.

Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) also known as AU-rich element RNA-binding protein 1 (AUF1) is a protein that in humans is encoded by the HNRNPD gene. Alternative splicing of this gene results in four transcript variants.

Synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP), also known as heterogeneous nuclear ribonucleoprotein (hnRNP) Q or NS1-associated protein-1 (NSAP-1), is a protein that in humans is encoded by the SYNCRIP gene. As the name implies, SYNCRIP is localized predominantly in the cytoplasm. It is evolutionarily conserved across eukaryotes and participates in several cellular and disease pathways, especially in neuronal and muscular development. In humans, there are three isoforms, all of which are associated in vitro with pre-mRNAs, mRNA splicing intermediates, and mature mRNA-protein complexes, including mRNA turnover.

Heterogeneous nuclear ribonucleoprotein F is a protein that in humans is encoded by the HNRNPF gene.

Heterogeneous nuclear ribonucleoprotein H is a protein that in humans is encoded by the HNRNPH1 gene.

Heterogeneous nuclear ribonucleoprotein A/B, also known as HNRNPAB, is a protein which in humans is encoded by the HNRNPAB gene. Although this gene is named HNRNPAB in reference to its first cloning as an RNA binding protein with similarity to HNRNP A and HNRNP B, it is not a member of the HNRNP A/B subfamily of HNRNPs, but groups together closely with HNRNPD/AUF1 and HNRNPDL.

Polypyrimidine tract-binding protein 1 is a protein that in humans is encoded by the PTBP1 gene.

<span class="mw-page-title-main">Prp24</span>

Prp24 is a protein part of the pre-messenger RNA splicing process and aids the binding of U6 snRNA to U4 snRNA during the formation of spliceosomes. Found in eukaryotes from yeast to E. coli, fungi, and humans, Prp24 was initially discovered to be an important element of RNA splicing in 1989. Mutations in Prp24 were later discovered in 1991 to suppress mutations in U4 that resulted in cold-sensitive strains of yeast, indicating its involvement in the reformation of the U4/U6 duplex after the catalytic steps of splicing.

<span class="mw-page-title-main">RNA recognition motif</span>

RNA recognition motif, RNP-1 is a putative RNA-binding domain of about 90 amino acids that are known to bind single-stranded RNAs. It was found in many eukaryotic proteins.

The RNA-binding Proteins Database (RBPDB) is a biological database of RNA-binding protein specificities that includes experimental observations of RNA-binding sites. The experimental results included are both in vitro and in vivo from primary literature. It includes four metazoan species, which are Homo sapiens, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans. RNA-binding domains included in this database are RNA recognition motif, K homology, CCCH zinc finger, and more domains. As of 2021, the latest RBPDB release includes 1,171 RNA-binding proteins.

References

1 2 García-Mayoral MF, Hollingworth D, Masino L, et al. (April 2007). "The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation" (PDF). Structure. 15 (4): 485–98. doi:10.1016/j.str.2007.03.006. PMID 17437720.
↑ Musco G, Kharrat A, Stier G, et al. (September 1997). "The solution structure of the first KH domain of FMR1, the protein responsible for the fragile X syndrome". Nat. Struct. Biol. 4 (9): 712–6. doi:10.1038/nsb0997-712. PMID 9302998. S2CID 11166126.
↑ Baber JL, Libutti D, Levens D, Tjandra N (June 1999). "High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor". J. Mol. Biol. 289 (4): 949–62. doi:10.1006/jmbi.1999.2818. PMID 10369774.
1 2 Grishin NV (February 2001). "KH domain: one motif, two folds". Nucleic Acids Res. 29 (3): 638–43. doi:10.1093/nar/29.3.638. PMC 30387 . PMID 11160884.
1 2 3 Valverde R, Edwards L, Regan L (June 2008). "Structure and function of KH domains". FEBS J. 275 (11): 2712–26. doi: 10.1111/j.1742-4658.2008.06411.x . PMID 18422648.

This article incorporates text from the public domain Pfam and InterPro: IPR004088

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[pmid17437720-1] 1 2 García-Mayoral MF, Hollingworth D, Masino L, et al. (April 2007). "The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation" (PDF). Structure. 15 (4): 485–98. doi:10.1016/j.str.2007.03.006. PMID 17437720.

[pmid9302998-2] Musco G, Kharrat A, Stier G, et al. (September 1997). "The solution structure of the first KH domain of FMR1, the protein responsible for the fragile X syndrome". Nat. Struct. Biol. 4 (9): 712–6. doi:10.1038/nsb0997-712. PMID 9302998. S2CID 11166126.

[pmid10369774-3] Baber JL, Libutti D, Levens D, Tjandra N (June 1999). "High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor". J. Mol. Biol. 289 (4): 949–62. doi:10.1006/jmbi.1999.2818. PMID 10369774.

[pmid11160884-4] 1 2 Grishin NV (February 2001). "KH domain: one motif, two folds". Nucleic Acids Res. 29 (3): 638–43. doi:10.1093/nar/29.3.638. PMC 30387 . PMID 11160884.

[pmid18422648-5] 1 2 3 Valverde R, Edwards L, Regan L (June 2008). "Structure and function of KH domains". FEBS J. 275 (11): 2712–26. doi: 10.1111/j.1742-4658.2008.06411.x . PMID 18422648.

[1]

[2]

[3]

[4]

[5]