K homology (KH) RNA-binding domain, type I; KH binds single-stranded RNA or DNA. It is found in a wide variety of proteins including ribosomal proteins, transcription factors and post-transcriptional modifiers of mRNA. There are two different KH domains that belong to different protein folds, but they share a single KH motif. The KH motif is folded into a beta alpha alpha beta unit. In addition to the core, type II KH domains (e.g. ribosomal protein S3) include an N-terminal extension and type I KH domains (e.g. hnRNP K) contain a C-terminal extension. Some KH-I superfamily members contain a divergent KH domain that lacks the RNA-binding GXXG motif. Some others have a mutated GXXG motif which may or may not have nucleic acid binding ability.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 134 KRILRLDLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLKGKPGYEHLNEQLHILIEADLP 213
Cdd:cd22467   1 KKVLRLDVPVDKYPNFNFVGRILGPRGNSLKRVEATTGCRVFIRGRGSIKDTAKEEKLRDKPGYEHLNEPLHVLIEAELP 80

                        90       100
                ....*....|....*....|.
gi 30680583 214 IDIVDIKLRQAQEIIEELVKP 234
Cdd:cd22467  81 ANIIDARLQHAQEIIEDLLKP 101

type I K homology (KH) RNA-binding domain found in Oryza sativa SPL11-interacting protein 1 (SPIN1) and similar proteins; SPIN1 is a K homology domain protein negatively regulated and ubiquitinated by the E3 ubiquitin ligase SPL11. It is involved in flowering time control in rice. SPIN1 binds DNA and RNA in vitro.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 134 KRILRLDLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLKGKPGYEHLNEQLHILIEADLP 213
Cdd:cd22467   1 KKVLRLDVPVDKYPNFNFVGRILGPRGNSLKRVEATTGCRVFIRGRGSIKDTAKEEKLRDKPGYEHLNEPLHVLIEAELP 80

                        90       100
                ....*....|....*....|.
gi 30680583 214 IDIVDIKLRQAQEIIEELVKP 234
Cdd:cd22467  81 ANIIDARLQHAQEIIEDLLKP 101

Homodimerization region of STAR domain protein; This family is the homodimerization domain of quaking proteins. Quaking-dimer is a helix-turn-helix dimer with an additional helix in the turn region. dimerization is required for adequate RNA-binding. Quaking is a prototypical member of the STAR (signal transducer and activator of RNA) protein family, which plays key roles in post-transcriptional gene regulation by controlling mRNA translation, stability and splicing. STAR_dimer is the homodimerization domain, Qua1 of the STAR domain of a series of proteins referred to as STAR/GSG, or Signal Transduction and Activation of RNA/GRP33, Sam68, GLD-1 family. These are conserved in higher eukaryotes and are RNA-binding transcriptional regulators. The STAR domain is a KH domain flanked by two homologous regions, Qua1 and Qua2. Qua1, this family, is the homodimerization domain, and the KH plus Qua2 is the RNA-binding region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 30680583    28 DSQYISQLLAEHQKLGPFMQVLPICSRLLNQEIFRITGMMPNQGFTD 74
Cdd:pfam16544   5 TPDYLAQLLKDKKQLAAFPNVFPHLERLLDEEISRVRGDLFNKGFGD 51

KH domain; KH motifs bind RNA in vitro. Autoantibodies to Nova, a KH domain protein, cause paraneoplastic opsoclonus ataxia.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 30680583   150 NFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPE 186
Cdd:pfam00013   9 SLVGLIIGKGGSNIKEIREETGAKIQIPPSESEGNER 45

type I K homology (KH) RNA-binding domain found in Oryza sativa SPL11-interacting protein 1 (SPIN1) and similar proteins; SPIN1 is a K homology domain protein negatively regulated and ubiquitinated by the E3 ubiquitin ligase SPL11. It is involved in flowering time control in rice. SPIN1 binds DNA and RNA in vitro.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 134 KRILRLDLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLKGKPGYEHLNEQLHILIEADLP 213
Cdd:cd22467   1 KKVLRLDVPVDKYPNFNFVGRILGPRGNSLKRVEATTGCRVFIRGRGSIKDTAKEEKLRDKPGYEHLNEPLHVLIEAELP 80

                        90       100
                ....*....|....*....|.
gi 30680583 214 IDIVDIKLRQAQEIIEELVKP 234
Cdd:cd22467  81 ANIIDARLQHAQEIIEDLLKP 101

type I K homology (KH) RNA-binding domain found in protein quaking (Hqk) and similar proteins; Hqk, also called HqkI, is an RNA-binding protein that plays a central role in myelinization. It binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence and regulates target mRNA stability. It acts by regulating pre-mRNA splicing, mRNA export and protein translation. Hqk is a regulator of oligodendrocyte differentiation and maturation in the brain that may play a role in myelin and oligodendrocyte dysfunction in schizophrenia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 138 RLDLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLKGKPGYEHLNEQLHILIEADLPIDIV 217
Cdd:cd22465   5 KLYVPVKEYPDFNFVGRILGPRGLTAKQLEAETGCKIMVRGKGSMRDKKKEEQNRGKPNWEHLNEDLHVLITVEDAQNRA 84

                        90
                ....*....|....*..
gi 30680583 218 DIKLRQAQEIIEELVKP 234
Cdd:cd22465  85 EIKLKRAVEEVKKLLVP 101

type I K homology (KH) RNA-binding domain found in Drosophila protein held out wings (how) and similar proteins; How, also called KH domain protein KH93F, or protein muscle-specific, or protein Struthio, or protein wings held out (who), or Quaking-related 93F (qkr93F), is an RNA-binding protein involved in the control of muscular and cardiac activity. It is required for integrin-mediated cell-adhesion in wing blade. It plays essential roles during embryogenesis, in late stages of somatic muscle development, for myotube migration and during metamorphosis for muscle reorganization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 132 PVKRILRLDLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLKGKPGYEHLNEQLHILIEAD 211
Cdd:cd22466   3 SVTLSEKVYVPVKEHPDYNFVGRILGPRGMTAKQLEQETGCKIMVRGKGSMRDKKKEDLNRGKPNWEHLNDELHVLITVE 82

                        90       100
                ....*....|....*....|...
gi 30680583 212 LPIDIVDIKLRQAQEIIEELVKP 234
Cdd:cd22466  83 DTENRAKVKLQRAVEEVRKLLVP 105

type I K homology (KH) RNA-binding domain found in KH domain-containing, RNA-binding, signal transduction-associated protein 1 (KHDRBS1) and similar proteins; KHDRBS1, also called GAP-associated tyrosine phosphoprotein p62, or Src-associated in mitosis 68 kDa protein, or Sam68, or p21 Ras GTPase-activating protein-associated p62, or p68, is an RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. It binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. It also binds poly(A). KHDRBS1 acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. It is recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 138 RLDLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLK--GKPGYEHLNEQLHILIEADLPID 215
Cdd:cd22468   8 RILIPVKQYPKFNFVGKILGPQGNTIKRLQEETGAKISVLGKGSMRDKAKEEELRkgGDPKYAHLNMDLHVFIEVFGPPC 87

                        90
                ....*....|....*....
gi 30680583 216 IVDIKLRQAQEIIEELVKP 234
Cdd:cd22468  88 EAYARMAHAMEEVKKFLVP 106

type I K homology (KH) RNA-binding domain found in KH domain-containing, RNA-binding, signal transduction-associated protein 2 (KHDRBS2) and similar proteins; KHDRBS2, also called Sam68-like mammalian protein 1, or SLM-1, is an RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. It binds both poly(A) and poly(U) homopolymers. KHDRBS2 may function as an adapter protein for Src kinases during mitosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 129 SSYPVKRILRLDLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLK--GKPGYEHLNEQLHI 206
Cdd:cd22469   1 SNKNIKLSERVLIPVKQYPKFNFVGKLLGPRGNSLKRLQEETGAKMSILGKGSMRDKAKEEELRksGEAKYAHLSDELHV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 30680583 207 LIEADLPIDIVDIKLRQAQEIIEELVKPvdESQDYIKRQQ 246
Cdd:cd22469  81 LIEVFAPPGEAYSRMSHALEEIKKFLVP--DYNDEIRQEQ 118

type I K homology (KH) RNA-binding domain found in KH domain-containing, RNA-binding, signal transduction-associated protein 3 (KHDRBS3) and similar proteins; KHDRBS3, also called RNA-binding protein T-Star, or Sam68-like mammalian protein 2, or SLM-2, or Sam68-like phosphotyrosine protein, is an RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. It binds optimally to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. It also binds poly(A). KHDRBS3 may play a role as a negative regulator of cell growth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30680583 141 LPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSIKDPEKEEKLK--GKPGYEHLNEQLHILIEADLPIDIVD 218
Cdd:cd22470  15 IPVKQFPKFNFVGKLLGPRGNSLKRLQEETLTKMSILGKGSMRDKAKEEELRksGEAKYFHLNDDLHVLIEVFAPPAEAY 94

                        90
                ....*....|....*.
gi 30680583 219 IKLRQAQEIIEELVKP 234
Cdd:cd22470  95 ARMGHALEEIKKFLIP 110

Homodimerization region of STAR domain protein; This family is the homodimerization domain of quaking proteins. Quaking-dimer is a helix-turn-helix dimer with an additional helix in the turn region. dimerization is required for adequate RNA-binding. Quaking is a prototypical member of the STAR (signal transducer and activator of RNA) protein family, which plays key roles in post-transcriptional gene regulation by controlling mRNA translation, stability and splicing. STAR_dimer is the homodimerization domain, Qua1 of the STAR domain of a series of proteins referred to as STAR/GSG, or Signal Transduction and Activation of RNA/GRP33, Sam68, GLD-1 family. These are conserved in higher eukaryotes and are RNA-binding transcriptional regulators. The STAR domain is a KH domain flanked by two homologous regions, Qua1 and Qua2. Qua1, this family, is the homodimerization domain, and the KH plus Qua2 is the RNA-binding region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 30680583    28 DSQYISQLLAEHQKLGPFMQVLPICSRLLNQEIFRITGMMPNQGFTD 74
Cdd:pfam16544   5 TPDYLAQLLKDKKQLAAFPNVFPHLERLLDEEISRVRGDLFNKGFGD 51

K homology RNA-binding domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 30680583    150 NFVGRLLGPRGNSLKRVEATTGCRVYIRGKGSikdPEKEEKLKGKP 195
Cdd:smart00322  12 DKVGLIIGKGGSTIKKIEEETGVKIDIPGPGS---EERVVEITGPP 54

second type I K homology (KH) RNA-binding domain found in insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and similar proteins; IGF2BP1, also called IGF2 mRNA-binding protein 1 (IMP-1), or coding region determinant-binding protein (CRD-BP), or IGF-II mRNA-binding protein 1, or VICKZ family member 1 (VICKZ1), or zipcode-binding protein 1 (ZBP-1), is an RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. It regulates localized beta-actin/ACTB mRNA translation, a crucial process for cell polarity, cell migration and neurite outgrowth. IGF2BP1 can form homodimers and heterodimers with IGF2BP1 and IGF2BP3. It contains four K-homology (KH) RNA-binding domains which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. The model corresponds to the second one.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 30680583 140 DLPVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIRGKG--SIKDPEKEEKLKG 193
Cdd:cd22493   4 EVPLKILAHNNFVGRLIGKEGRNLKKVEQDTETKITISPLQdlTLYNPERTITVKG 59

second type I K homology (KH) RNA-binding domain found in insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and similar proteins; IGF2BP3, also called IGF2 mRNA-binding protein 3 (IMP-3), or hepatocellular carcinoma autoantigen p62, or IGF-II mRNA-binding protein 3, or VICKZ family member 3 (VICKZ3), or KH domain-containing protein overexpressed in cancer, or KOC, is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. It acts as an RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. IGF2BP3 binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. It also binds to beta-actin/ACTB and MYC transcripts. IGF2BP3 can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP2 in an RNA-dependent manner. IGF2BP3 contains four K-homology (KH) RNA-binding domains which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. The model corresponds to the second one.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 30680583 142 PVDTYPNFNFVGRLLGPRGNSLKRVEATTGCRVYIR--GKGSIKDPEKEEKLKG 193
Cdd:cd22495   1 PLKILAHNNFVGRLIGKEGRNLKKIEQDTDTKITISplQDLTLYNPERTITVKG 54