SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1174697597 184 FFKNQLPVTCGSIKGILNHDKLAKG--EKCIKVKDQWFTPAEFEKFAGKEKSRNWKSSIRCENITLGKLIQEGHL 256
Cdd:pfam01342   2 FDSPVLPVTCGAAKGLLHKKKFKQGisGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

PHD finger found in the transcriptional intermediary factor 1 (TIF1) family and similar proteins; The TIF1 family of transcriptional cofactors includes TIF1alpha (TRIM24), TIF1beta (TRIM28), TIF1gamma (TRIM33), and TIF1delta (TRIM66), which are characterized by an N-terminal RING-finger B-box coiled-coil (RBCC/TRIM) motif and plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha, TIF1beta, and TIF1delta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. TIF1alpha and TIF1beta bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. In contrast, TIF1delta appears to lack nuclear receptor- and KRAB-binding activity. Moreover, TIF1delta is specifically involved in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta, and gamma. It cannot bind to nuclear receptors (NRs). This family also includes Sp100/Sp140 family proteins, the nuclear body SP100 and SP140. Sp110 is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. SP140 is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus viral infectivity factor (Vif) protein. Both Sp110 and Sp140 contain a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1174697597 413 ECYICEDVGDLVVCDHCPKSFHPNCHLPHIEEammSDNNPWMCTFC 458
Cdd:cd15541     1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIPE---FPSGEWSCSLC 43

SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1174697597 321 DKENATFEVSCGQ--------FL--GTRGLSIRTEDKWMSPVEFVMEATSQTDATWRKDIIYNEEPLNALIEAKVL 386
Cdd:pfam01342   1 DFDSPVLPVTCGAakgllhkkKFkqGISGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1174697597 184 FFKNQLPVTCGSIKGILNHDKLAKG--EKCIKVKDQWFTPAEFEKFAGKEKSRNWKSSIRCENITLGKLIQEGHL 256
Cdd:pfam01342   2 FDSPVLPVTCGAAKGLLHKKKFKQGisGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

Bromodomain. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597 488 ECQYLLLFLRN--TDKEQIFNTNP-ELNLENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAE 564
Cdd:cd04369     4 KLRSLLDALKKlkRDLSEPFLEPVdPKEAPDYYEVIKNPMDLSTIKKKLKNGEYKSLEEFEADVRLIFSNAKTYNGPGSP 83

                          90
                  ....*....|....*.
gi 1174697597 565 FLEIGKRLKETFDKEF 580
Cdd:cd04369    84 IYKDAKKLEKLFEKLL 99

PHD finger found in the transcriptional intermediary factor 1 (TIF1) family and similar proteins; The TIF1 family of transcriptional cofactors includes TIF1alpha (TRIM24), TIF1beta (TRIM28), TIF1gamma (TRIM33), and TIF1delta (TRIM66), which are characterized by an N-terminal RING-finger B-box coiled-coil (RBCC/TRIM) motif and plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha, TIF1beta, and TIF1delta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. TIF1alpha and TIF1beta bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. In contrast, TIF1delta appears to lack nuclear receptor- and KRAB-binding activity. Moreover, TIF1delta is specifically involved in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta, and gamma. It cannot bind to nuclear receptors (NRs). This family also includes Sp100/Sp140 family proteins, the nuclear body SP100 and SP140. Sp110 is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. SP140 is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus viral infectivity factor (Vif) protein. Both Sp110 and Sp140 contain a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1174697597 413 ECYICEDVGDLVVCDHCPKSFHPNCHLPHIEEammSDNNPWMCTFC 458
Cdd:cd15541     1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIPE---FPSGEWSCSLC 43

HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597  11 QLQQFFHSRKTELS-CLENPQTFLSQLRDYNLIPEDRYKKVIKMK-SKDRRRMAIYEFLDWMERERSehiPLFWRCVFKE 88
Cdd:pfam03172   4 ALFQHFKENKVEIAyAIKKPFPFLEGLRDHSFITEKMYKESLEACrNLVPVQRVVYNVLSELEKTFS---LSLLEALFSD 80

                          90
                  ....*....|....*.
gi 1174697597  89 IILSQYPIFRLMRNSL 104
Cdd:pfam03172  81 VNLKEYPDLIEILKSF 96

Transcription factor involved in chromatin remodeling, contains bromodomain [Chromatin structure and dynamics / Transcription];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597 488 ECQYLLLFLRNTDKEQIFNTN-------PELNLENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNR 560
Cdd:COG5076   146 DNKAIAKFKKQLFLRDGRFLSsiflglpSKREYPDYYEIIKSPMDLLTIQKKLKNGRYKSFEEFVSDLNLMFDNCKLYNG 225

                          90       100
                  ....*....|....*....|..
gi 1174697597 561 DNAEFLEIGKRLKETFDKEFKK 582
Cdd:COG5076   226 PDSSVYVDAKELEKYFLKLIEE 247

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1174697597  414 CYICEDV---GDLVVCDHCPKSFHPNCHLPHIEEAMMSDNnpWMCTFC 458
Cdd:smart00249   2 CSVCGKPddgGELLQCDGCDRWYHQTCLGPPLLEEEPDGK--WYCPKC 47

SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1174697597 184 FFKNQLPVTCGSIKGILNHDKLAKG--EKCIKVKDQWFTPAEFEKFAGKEKSRNWKSSIRCENITLGKLIQEGHL 256
Cdd:pfam01342   2 FDSPVLPVTCGAAKGLLHKKKFKQGisGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

Bromodomain. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597 488 ECQYLLLFLRN--TDKEQIFNTNP-ELNLENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAE 564
Cdd:cd04369     4 KLRSLLDALKKlkRDLSEPFLEPVdPKEAPDYYEVIKNPMDLSTIKKKLKNGEYKSLEEFEADVRLIFSNAKTYNGPGSP 83

                          90
                  ....*....|....*.
gi 1174697597 565 FLEIGKRLKETFDKEF 580
Cdd:cd04369    84 IYKDAKKLEKLFEKLL 99

Bromodomain. BDF1/BDF2 like subfamily, restricted to fungi, repeat I. BDF1 and BDF2 are yeast transcription factors involved in the expression of a wide range of genes, including snRNAs; they are required for sporulation and DNA repair and protect histone H4 from deacetylation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597 491 YLLLFLRNTD--KEQIFNTNP----ELNLENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAE 564
Cdd:cd05500     8 FLLSSIRSLKrlKDARPFLVPvdpvKLNIPHYPTIIKKPMDLGTIERKLKSNVYTSVEEFTADFNLMVDNCLTFNGPEHP 87

                          90
                  ....*....|....
gi 1174697597 565 FLEIGKRLKETFDK 578
Cdd:cd05500    88 VSQMGKRLQAAFEK 101

Bromodomain; Acf1_like or BAZ1A_like subfamily. Bromo adjacent to zinc finger 1A (BAZ1A) was identified as a novel human bromodomain gene by cDNA library screening. The Drosophila homologue, Acf1, is part of the CHRAC (chromatin accessibility complex) and regulates ISWI-induced nucleosome remodeling. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1174697597 515 NYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAEFLEIGKRLKETFDKEFKK 582
Cdd:cd05504    44 DYYDIIKKPMDLGTIKEKLNMGEYKLAEEFLSDIQLVFSNCFLYNPEHTSVYKAGTRLQRFFIKRCRK 111

Bromodomain; Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597 489 CQYLLLFLRNTDKEQIF-NTNPELNLENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAEFLE 567
Cdd:pfam00439   1 CLEILDKLMEHPIAAPFlEPVDPDEYPDYYSVIKKPMDLSTIKKKLENGEYKSLAEFLADVKLIFSNARTYNGPGSVIYK 80

                  ....
gi 1174697597 568 IGKR 571
Cdd:pfam00439  81 AAEK 84

HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597  11 QLQQFFHSRKTELS-CLENPQTFLSQLRDYNLIPEDRYKKVIKMK-SKDRRRMAIYEFLDWMERERSehiPLFWRCVFKE 88
Cdd:pfam03172   4 ALFQHFKENKVEIAyAIKKPFPFLEGLRDHSFITEKMYKESLEACrNLVPVQRVVYNVLSELEKTFS---LSLLEALFSD 80

                          90
                  ....*....|....*.
gi 1174697597  89 IILSQYPIFRLMRNSL 104
Cdd:pfam03172  81 VNLKEYPDLIEILKSF 96

SAND domain; The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerization. This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1174697597 321 DKENATFEVSCGQ--------FL--GTRGLSIRTEDKWMSPVEFVMEATSQTDATWRKDIIYNEEPLNALIEAKVL 386
Cdd:pfam01342   1 DFDSPVLPVTCGAakgllhkkKFkqGISGKCIQNEDSWLTPKEFEIEGGKASSKDWKRSIRCGGKPLRELIEKGLL 76

Bromodomain, BAZ2A/BAZ2B_like subfamily. Bromo adjacent to zinc finger 2A (BAZ2A) and 2B (BAZ2B) were identified as a novel human bromodomain gene by cDNA library screening. BAZ2A is also known as Tip5 (Transcription termination factor I-interacting protein 5) and hWALp3. The proteins may play roles in transcriptional regulation. Human Tip5 is part of a complex termed NoRC (nucleolar remodeling complex), which induces nucleosome sliding and may play a role in the regulation of the rDNA locus. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1174697597 516 YRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAEFLEIGKRLKETFDK 578
Cdd:cd05503    33 YRKIIKKPMDFSTIREKLESGQYKTLEEFAEDVRLVFDNCETFNEDDSEVGRAGHNMRKFFEK 95

Bromodomain; tif1_like subfamily. Tif1 (transcription intermediary factor 1) is a member of the tripartite motif (TRIM) protein family, which is characterized by a particular domain architecture. It functions by recruiting coactivators and/or corepressors to modulate transcription. Vertebrate Tif1-gamma, also labeled E3 ubiquitin-protein ligase TRIM33, plays a role in the control of hematopoiesis. Its homologue in Xenopus laevis, Ectodermin, has been shown to function in germ-layer specification and control of cell growth during embryogenesis. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597 489 CQYLLLFLRNTDKEQIFNTNPELNLENYRCFVETPMWLGKITDKLQE---NQYKTVGQFESDIQLIFSNCGCYNRDNAEF 565
Cdd:cd05502     9 CERLLLELYCHELSLPFHEPVSPSVPNYYKIIKTPMDLSLIRKKLQPkspQHYSSPEEFVADVRLMFKNCYKFNEEDSEV 88

                          90
                  ....*....|....*....
gi 1174697597 566 LEIGKRLKETFDKEFKKAF 584
Cdd:cd05502    89 AQAGKELELFFEEQLKEIL 107

PHD finger found in the Sp100/Sp140 family of nuclear body components; The Sp100/Sp140 family includes nuclear body proteins SP100, SP140, and similar proteins. Sp110, also termed interferon-induced protein 41/75, or speckled 110 kDa, or transcriptional coactivator Sp110, is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. Sp110 gene polymorphisms may be associated with susceptibility to tuberculosis in Chinese population. Sp110 contains a Sp100-like domain, a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD). SP140, also termed lymphoid-restricted homolog of Sp100 (LYSp100), or nuclear autoantigen Sp-140, or speckled 140 kDa, is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus's viral infectivity factor (Vif) protein. Sp140 contains a nuclear localization signal, a dimerization domain (HSR or CARD domain), a SAND domain, a PHD finger, and a BRD.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1174697597 413 ECYICEDVGDLVVCDHCPKSFHPNCHLPHIEEAMMsdnnPWMCTFC 458
Cdd:cd15626     1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRS----PWSCTFC 42

PHD finger found in transcriptional intermediary factor 1 delta (TIF1delta); TIF1delta, also termed tripartite motif-containing protein 66 (TRIM66), is a novel heterochromatin protein 1 (HP1)-interacting member of the transcriptional intermediary factor1 (TIF1) family expressed by elongating spermatids. Like other TIF1 proteins, TIF1delta displays a potent trichostatin A (TSA)-sensitive repression function; TSA is a specific inhibitor of histone deacetylases. Moreover, TIF1delta plays an important role in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. It functions as a negative regulator of postmeiotic genes acting through HP1 isotype gamma (HP1gamma) complex formation and centromere association. TIF1delta contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1174697597 410 NDDECYICEDVGDLVVCDHCPKSFHPNCHLPhieeAMMS-DNNPWMCTFC 458
Cdd:cd15625     1 NEDFCAVCLNGGELLCCDRCPKVFHLSCHVP----ALLSfPVGEWVCTLC 46

Transcription factor involved in chromatin remodeling, contains bromodomain [Chromatin structure and dynamics / Transcription];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174697597 488 ECQYLLLFLRNTDKEQIFNTN-------PELNLENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNR 560
Cdd:COG5076   146 DNKAIAKFKKQLFLRDGRFLSsiflglpSKREYPDYYEIIKSPMDLLTIQKKLKNGRYKSFEEFVSDLNLMFDNCKLYNG 225

                          90       100
                  ....*....|....*....|..
gi 1174697597 561 DNAEFLEIGKRLKETFDKEFKK 582
Cdd:COG5076   226 PDSSVYVDAKELEKYFLKLIEE 247

ADDz domain found in ATRX (alpha-thalassemia/mental retardation, X-linked); ADDz_ATRX is a PHD-like zinc finger domain of ATRX, which belongs to the SNF2 family of chromatin remodeling proteins. ATRX is a large chromatin-associated nuclear protein with two domains, ADDz_ATRX at the N-terminus, followed by a C-terminal ATPase/helicase domain. The ADDz_ATRX domain recognizes a specific methylated histone, and this interaction is required for heterochromatin localization of the ATRX protein. Missense mutations in either of the two ATRX domains lead to the X-linked alpha-thalassemia and mental retardation syndrome; however the mutations in the ADDz_ATRX domain produce a more severe disease phenotype that may also relate to disturbing unknown functions or interaction sites of this domain. The ADDz domain is also present in chromatin-associated proteins cytosine-5-methyltransferase 3 (Dnmt3); it is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1174697597 395 CRKCKAELKDKDNQKNDD----ECYICEDVGDLVVCDHCPKSFHPNC---HLPHIEEAMMSDNNPWMCTFC 458
Cdd:cd11726    30 CKSCLKFYNSGEFSKDEDgsdeYCRWCGQGGDLICCDFCPNVFCKKCikrNLGRAELSRIEESDKWKCFVC 100

PHD finger found in transcriptional intermediary factor 1 gamma (TIF1gamma); TIF1gamma, also termed tripartite motif-containing 33 (trim33), or ectodermin, or RFG7, or PTC7, is an E3-ubiquitin ligase that functions as a regulator of transforming growth factor beta (TGFbeta) signaling; it inhibits the Smad4-mediated TGFbeta response by interaction with Smad2/3 or ubiquitylation of Smad4. Moreover, TIF1gamma is an important regulator of transcription during hematopoiesis, as well as a key factor of tumorigenesis. Like other TIF1 family members, TIF1gamma also contains an intrinsic transcriptional silencing function. It can control erythroid cell fate by regulating transcription elongation. It can bind to the anaphase-promoting complex/cyclosome (APC/C) and promotes mitosis. TIF1gamma contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174697597 414 CYICEDVGDLVVCDHCPKSFHPNCHLPHIeeaMMSDNNPWMCTFC 458
Cdd:cd15624     2 CAVCQNGGDLLCCEKCPKVFHLTCHVPTL---LSFPSGDWICTFC 43

PHD finger 1 found in autoimmune regulator (AIRE); AIRE, also termed autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) protein, functions as a regulator of gene transcription in the thymus. It is essential for prevention of autoimmunity. AIRE plays a critical role in the induction of central tolerance. It promotes self-tolerance through tissue-specific antigen (TSA) expression. It also acts as an active regulator of chondrocyte differentiation. AIRE contains a homogeneously-staining region (HSR) or caspase-recruitment domain (CARD), a nuclear localization signal (NLS), a SAND (for Sp100, AIRE, nuclear phosphoprotein 41/75 or NucP41/75, and deformed epidermal auto regulatory factor 1 or Deaf1) domain, two plant homeodomain (PHD) fingers, and four LXXLL (where L stands for leucine) motifs. This model corresponds to the first PHD finger that recognizes the unmethylated tail of histone H3 and targets AIRE-dependent genes.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1174697597 413 ECYICEDVGDLVVCDHCPKSFHPNCHLPHIEEaMMSDNnpWMCTFC 458
Cdd:cd15539     1 ECAVCGDGGELLCCDGCPRAFHLACLVPPLTL-IPSGT--WRCSSC 43

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1174697597 414 CYICEDV---GDLVVCDHCPKSFHPNCHLPHIEEAMMSDNNpWMCTFCIFK 461
Cdd:pfam00628   2 CAVCGKSddgGELVQCDGCDDWFHLACLGPPLDPAEIPSGE-WLCPECKPK 51

PHD finger 2 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174697597 414 CYICEDVGDLVVCDHCPKSFHPNCHLPHIEEAmmsDNNPWMCTFC 458
Cdd:cd15532     2 CRVCKDGGELLCCDGCPSSYHLHCLNPPLAEI---PDGDWFCPRC 43

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1174697597  414 CYICEDV---GDLVVCDHCPKSFHPNCHLPHIEEAMMSDNnpWMCTFC 458
Cdd:smart00249   2 CSVCGKPddgGELLQCDGCDRWYHQTCLGPPLLEEEPDGK--WYCPKC 47

PHD finger found in transcription intermediary factor 1-beta (TIF1-beta); TIF1-beta, also termed Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), or KRAB-interacting protein 1 (KRIP-1), or nuclear co-repressor KAP-1, or RING finger protein 96, or tripartite motif-containing protein 28 (TRIM28), or E3 SUMO-protein ligase TRIM28, acts as a nuclear co-repressor that plays a role in transcription and in DNA damage response. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair. It also regulates CHD3 nucleosome remodeling during DNA double-strand break (DSB) response. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response. In addition, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase. TIF1-beta contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), which can interact with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and mediates homo- and heterodimerization, a plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region, which interact with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174697597 414 CYICEDVGDLVVCDHCPKSFHPNCHLPHIEEAMMSDnnpWMCTFC 458
Cdd:cd15623     2 CRVCQKAGALVMCDQCEFCFHLDCHLPALQEVPGED---WKCLLC 43

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1174697597 414 CYICEDVGD----LVVCDHCPKSFHPNCHLPHIEEAMmsDNNPWMCTFC 458
Cdd:cd15489     2 CIVCGKGGDlggeLLQCDGCGKWFHADCLGPPLSSFV--PNGKWICPVC 48

PHD finger 1 found in PHD finger protein1 (PHF1); PHF1, also termed polycomb-like protein 1 (PCL1), together with JARID2 and AEBP2, associates with the polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. PHF1 is essential in epigenetic regulation and genome maintenance. It acts as a dual reader of Lysine trimethylation at Lysine 36 of Histone H3 and Lysine 27 of Histone variant H3t. PHF1 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. Its Tudor domain selectively binds to histone H3K36me3. Moreover, PHF1 is required for efficient H3K27me3 and Hox gene silencing. It can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response. This model corresponds to the first PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1174697597 423 LVVCDHCPKSFHPNCHLPHIEEAMMSDNNPWMCTFC 458
Cdd:cd15500    16 LVNCEKCHHAYHQECHVPRVPLESAGDGDSWMCRQC 51

PHD finger 4 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fourth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174697597 414 CYICEDVGDLVVCDHCPKSFHPNChlphIEEAMMSDNNpWMCTFC 458
Cdd:cd15567     2 CFICSEGGSLICCESCPASFHPEC----LGLEPPPEGK-FYCEDC 41

PHD finger 1 found in bromodomain and PHD finger-containing transcription factor (BPTF); BPTF, also termed nucleosome-remodeling factor subunit BPTF, or fetal Alz-50 clone 1 protein (FAC1), or fetal Alzheimer antigen, functions as a transcriptional regulator that exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease. It interacts with the human orthologue of the Kelch-like Ech-associated protein (Keap1). Its function and subcellular localization can be regulated by Keap1. Moreover, BPTF is a novel DNA-binding protein that recognizes the DNA sequence CACAACAC and represses transcription through this site in a phosphorylation-dependent manner. Furthermore, BPTF interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity, which has been implicated in gene regulation in neurodegeneration. Some family members contain two or three plant homeodomain (PHD) fingers, which may be involved in complex formation with histone H3 trimethylated at K4 (H3K4me3). This family corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174697597 414 CYICEDVGDLVVCDHCPKSFHPNCHLPHIEEAMMSDnnpWMCTFC 458
Cdd:cd15559     2 CRVCHKLGDLLCCETCSAVYHLECVDPPLEEVPEED---WQCEVC 43

Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1174697597 511 LNLENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNR 560
Cdd:cd05497    35 LNLPDYHKIIKTPMDLGTIKKRLENNYYWSASECIQDFNTMFTNCYIYNK 84

Bromodomain, TFIID-like subfamily. Human TAFII250 (or TAF250) is the largest subunit of TFIID, a large multi-domain complex, which initiates the assembly of the transcription machinery. TAFII250 contains two bromodomains that specifically bind to acetylated histone H4. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1174697597 520 VETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAEF 565
Cdd:cd05511    37 IKRPMDLQTIRKKISKHKYQSREEFLEDIELIVDNSVLYNGPDSVY 82

Bromodomain, RACK7_like subfamily. RACK7 (also called human protein kinase C-binding protein) was identified as a potential tumor suppressor genes, it shares domain architecture with BS69/ZMYND11; both have been implicated in the regulation of cellular proliferation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1174697597 515 NYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAEFLEIGKRLKETFDKE 579
Cdd:cd05508    34 DYAQYVFKPMDLSTLEKNVRKKAYGSTDAFLADAKWILHNAIIYNGGDHKLTQAAKAIVKICEQE 98

PHD finger 2 found in PHD finger protein 12 (PHF12), yeast Rco1, and similar proteins; PHF12, also termed PHD factor 1 (Pf1), is a plant homeodomain (PHD) zinc finger-containing protein that bridges the transducin-like enhancer of split (TLE) corepressor to the mSin3A-histone deacetylase (HDAC)-complex, and further represses transcription at targeted genes. PHF12 also interacts with MRG15 (mortality factor-related genes on chromosome 15), a member of the mortality factor (MORF) family of proteins implicated in regulating cellular senescence. PHF12 contains two plant homeodomain (PHD) zinc fingers followed by a polybasic region. The PHD fingers function downstream of phosphoinositide signaling triggered by the interaction between polybasic regions and phosphoinositides. This subfamily also includes yeast transcriptional regulatory protein Rco1 and similar proteins. Rco1 is a component of the Rpd3S histone deacetylase complex that plays an important role at actively transcribed genes. Rco1 contains two PHD fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174697597 414 CYICEDVGD---LVVCDHCPKSFHPNCHLPHIeeAMMSDNNPWMC 455
Cdd:cd15534     2 CFKCNRSCRvapLIQCDYCPLLFHLDCLDPPL--THPPATGRWMC 44

PHD finger 4 found in nuclear SET domain-containing protein 2 (NSD2); NSD2, also termed histone-lysine N-methyltransferase NSD2, or multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, a high mobility group (HMG) box, five PHD (plant-homeodomain) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD fingers mediate chromatin interaction and recognition of histone marks. This model corresponds to the fourth PHD finger.

                          10        20
                  ....*....|....*....|....
gi 1174697597 414 CYICEDVGDLVVCDHCPKSFHPNC 437
Cdd:cd15657     2 CFVCSKGGSLLCCESCPAAFHPDC 25

PHD finger found in protein kinase C-binding protein 1 (PRKCBP1); PRKCBP1, also termed cutaneous T-cell lymphoma-associated antigen se14-3 (CTCL-associated antigen se14-3), or Rack7, or zinc finger MYND domain-containing protein 8 (ZMYND8), is a novel receptor for activated C-kinase (RACK)-like protein that may play an important role in the activation and regulation of PKC-beta I, and the PKC signaling cascade. It also has been identified as a formin homology-2-domain containing protein 1 (FHOD1)-binding protein that may be involved in FHOD1-regulated actin polymerization and transcription. Moreover, PRKCBP1 may function as a REST co-repressor 2 (RCOR2) interacting factor; the RCOR2/ZMYND8 complex which might be involved in the regulation of neural differentiation. PRKCBP1 contains a plant homeodomain (PHD) finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174697597 414 CYICEDVGDLVVCDHCPKSFHPNChlphIEEAMMSDNNpWMCTFC 458
Cdd:cd15538     2 CWRCHKEGQVLCCSLCPRVYHKKC----LKLTSEPDED-WVCPEC 41

Bromodomain, SNF2-like subfamily, specific to fungi. SNF2 is a yeast protein involved in transcriptional activation, it is the catalytic component of the SWI/SNF ATP-dependent chromatin remodeling complex. The protein is essential for the regulation of gene expression (both positive and negative) of a large number of genes. The SWI/SNF complex changes chromatin structure by altering DNA-histone contacts within the nucleosome, which results in a re-positioning of the nucleosome and facilitates or represses the binding of gene-specific transcription factors. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1174697597 504 IFNTNPELNL-ENYRCFVETPMWLGKITDKLQENQYKTVGQFESDIQLIFSNCGCYNRDNAEFLEIGKRLKETFDKEF 580
Cdd:cd05519    26 LFLEKPSKKLyPDYYVIIKRPIALDQIKRRIEGRAYKSLEEFLEDFHLMFANARTYNQEGSIVYEDAVEMEKAFKKKY 103

ATRX, Dnmt3 and Dnmt3l PHD-like zinc finger domain (ADDz); The ADDz zinc finger domain is present in the chromatin-associated proteins cytosine-5-methyltransferase 3 (Dnmt3) and ATRX, a SNF2 type transcription factor protein. The Dnmt3 family includes two active DNA methyltransferases, Dnmt3a and -3b, and one regulatory factor Dnmt3l. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The ADDz domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1174697597 395 CRKCKAELKDKDNQKNDD----ECYICEDVGDLVVCDH--CPKSFHPNCHLPHI---EEAMMSDNNPWMCTFC 458
Cdd:cd11672    25 CKNCKKYFLSDDISYDDDgyqsYCRICCEGGNLLCCGNnfCHRCFCKECVDRLVgpgELSTMDENNQWYCYIC 97

PHD finger 2 found in autoimmune regulator (AIRE); AIRE, also termed autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) protein, functions as a regulator of gene transcription in the thymus. It is essential for prevention of autoimmunity. AIRE plays a critical role in the induction of central tolerance. It promotes self-tolerance through tissue-specific antigen (TSA) expression. It also acts as an active regulator of chondrocyte differentiation. AIRE contains a homogeneously-staining region (HSR) or caspase-recruitment domain (CARD), a nuclear localization signal (NLS), a SAND (for Sp100, AIRE, nuclear phosphoprotein 41/75 or NucP41/75, and deformed epidermal auto regulatory factor 1 or Deaf1) domain, two plant homeodomain (PHD) fingers, and four LXXLL (where L stands for leucine) motifs. This model corresponds to the second PHD finger that may play a critical role in the activation of gene transcription.

                          10        20
                  ....*....|....*....|....*....
gi 1174697597 413 ECYICED-VGDLVVCDHCPKSFHPNCHLP 440
Cdd:cd15540     1 RCGVCRGgRGDLLRCPQCLQAFHWHCHFP 29