Zic proteins zinc finger domain; This is the ZF1 (Zinc Finger 1) domain found in Zic family proteins found in Eukaryotes. In humans, there are five members of the Zic family that are involved in human congenital anomalies. One of them, ZIC3, causes X-linked heterotaxy (HTX1), which is a left-right axis disturbance that manifests as variable combinations of heart malformation, altered lung lobation, splenic abnormality and gastrointestinal malrotation. Zic faily proteins contain multiple zinc finger domains (ZFD), which are generally composed of five tandemly repeated C2H2 zinc finger (ZF) motifs. Sequence comparison analysis reveal that this N-terminal ZF (ZF1) domain of the Zic zinc finger domains is unique in that it possesses more amino acid residues (6-38 amino acids) between the two cysteine residues of the C2H2 motif compared to Gli and Glis ZF1s or any of the other ZFs (ZF2-5) in the Gli/Glis/Zic superfamily of proteins. Mutations in cysteine 253 (C253S) or histidine 286 (H286R) in ZIC3 ZF1, which are found in heterotaxy patients, result in extranuclear localization of the mutant ZIC3 protein. Furthermore, mutations in the evolutionarily conserved amino acid residues (C253, W255, C268, H281 and H286) of ZF1 generally impair nuclear localization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 49227339   202 QCIKQELICKWIDPEQlGDPKKCCSKTFSTMHELVTHVSTEHVGGP 247
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

Zic proteins zinc finger domain; This is the ZF1 (Zinc Finger 1) domain found in Zic family proteins found in Eukaryotes. In humans, there are five members of the Zic family that are involved in human congenital anomalies. One of them, ZIC3, causes X-linked heterotaxy (HTX1), which is a left-right axis disturbance that manifests as variable combinations of heart malformation, altered lung lobation, splenic abnormality and gastrointestinal malrotation. Zic faily proteins contain multiple zinc finger domains (ZFD), which are generally composed of five tandemly repeated C2H2 zinc finger (ZF) motifs. Sequence comparison analysis reveal that this N-terminal ZF (ZF1) domain of the Zic zinc finger domains is unique in that it possesses more amino acid residues (6-38 amino acids) between the two cysteine residues of the C2H2 motif compared to Gli and Glis ZF1s or any of the other ZFs (ZF2-5) in the Gli/Glis/Zic superfamily of proteins. Mutations in cysteine 253 (C253S) or histidine 286 (H286R) in ZIC3 ZF1, which are found in heterotaxy patients, result in extranuclear localization of the mutant ZIC3 protein. Furthermore, mutations in the evolutionarily conserved amino acid residues (C253, W255, C268, H281 and H286) of ZF1 generally impair nuclear localization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 49227339   202 QCIKQELICKWIDPEQlGDPKKCCSKTFSTMHELVTHVSTEHVGGP 247
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

Zinc finger, C2H2 type; The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter.

                          10        20
                  ....*....|....*....|...
gi 49227339   345 YLCKLCDKSYTHPSSLRKHMKVH 367
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRTH 23

Zic proteins zinc finger domain; This is the ZF1 (Zinc Finger 1) domain found in Zic family proteins found in Eukaryotes. In humans, there are five members of the Zic family that are involved in human congenital anomalies. One of them, ZIC3, causes X-linked heterotaxy (HTX1), which is a left-right axis disturbance that manifests as variable combinations of heart malformation, altered lung lobation, splenic abnormality and gastrointestinal malrotation. Zic faily proteins contain multiple zinc finger domains (ZFD), which are generally composed of five tandemly repeated C2H2 zinc finger (ZF) motifs. Sequence comparison analysis reveal that this N-terminal ZF (ZF1) domain of the Zic zinc finger domains is unique in that it possesses more amino acid residues (6-38 amino acids) between the two cysteine residues of the C2H2 motif compared to Gli and Glis ZF1s or any of the other ZFs (ZF2-5) in the Gli/Glis/Zic superfamily of proteins. Mutations in cysteine 253 (C253S) or histidine 286 (H286R) in ZIC3 ZF1, which are found in heterotaxy patients, result in extranuclear localization of the mutant ZIC3 protein. Furthermore, mutations in the evolutionarily conserved amino acid residues (C253, W255, C268, H281 and H286) of ZF1 generally impair nuclear localization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 49227339   202 QCIKQELICKWIDPEQlGDPKKCCSKTFSTMHELVTHVSTEHVGGP 247
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

FOG: Zn-finger [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49227339 221 PKKCCSKTFSTMHELVTHVSTEHVGGPEQCNHICFWEECPresKPFKAKYKLVNHIRVHTGEKPFACPFPGCGKVFARSE 300
Cdd:COG5048 291 KSKQCNISFSRSSPLTRHLRSVNHSGESLKPFSCPYSLCG---KLFSRNDALKRHILLHTSISPAKEKLLNSSSKFSPLL 367

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49227339 301 NLKIHKRTH-----TGEKPFLCEFEGCDRRFANSSDRKKHMHVHTSDKPYLCK--LCDKSYTHPSSLRKHMKVHEDQAPI 373
Cdd:COG5048 368 NNEPPQSLQqykdlKNDKKSETLSNSCIRNFKRDSNLSLHIITHLSFRPYNCKnpPCSKSFNRHYNLIPHKKIHTNHAPL 447

FOG: Zn-finger [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49227339 288 PFPGCGKVFARSENLKIHKRTHTGEKPFLCEFEGCDRRFANSSDRKKHMHVHTSDKPYLckLCDKSYTHPSSLRKHMKVH 367
Cdd:COG5048  35 SCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELSRHLRTHHNNPSDL--NSKSLPLSNSKASSSSLSS 112

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 49227339 368 EDQAPIADSSPAGSSGYESSTPSSLISPCSETHSTLSPDSAALNSSGHNSLTSNFN 423
Cdd:COG5048 113 SSSNSNDNNLLSSHSLPPSSRDPQLPDLLSISNLRNNPLPGNNSSSVNTPQSNSLH 168

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*...
gi 49227339   301 NLKIHKRTHTGEKPFLCEFegCDRRFAN 328
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPE--CGKSFKS 26