PDZ domain of PDZ domain-containing protein GIPC3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC3, and related domains. GIPC3 (also known as C19orf64) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837 313 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPKSQPF 392
Cdd:cd23079    1 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIIDRIKAVCVGDHIEAINDQSIVGCRHYEVAKMLRELPKSQPF 80

                 ....*....
gi 537152837 393 TLRLVQPRR 401
Cdd:cd23079   81 TLRLVEPKR 89

PDZ domain of PDZ domain-containing protein GIPC3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC3, and related domains. GIPC3 (also known as C19orf64) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837 313 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPKSQPF 392
Cdd:cd23079    1 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIIDRIKAVCVGDHIEAINDQSIVGCRHYEVAKMLRELPKSQPF 80

                 ....*....
gi 537152837 393 TLRLVQPRR 401
Cdd:cd23079   81 TLRLVEPKR 89

HMG (high mobility group) box;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837  100 PKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAY 167
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAEKEKARYEKEHPEY 68

GIPC-homology 2 (GH2) domain found in the GIPC family; The GIPC family includes PDZ domain-containing proteins, GIPC1 (also called GAIP C-terminus-interacting protein, RGS-GAIP-interacting protein, RGS19-interacting protein 1, RGS19IP1, synectin, tax interaction protein 2, or TIP-2), GIPC2, and GIPC3, which may act as scaffold proteins linking heterotrimeric G-proteins to seven-transmembrane-type WNT receptor or to receptor tyrosine kinases. They might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion. GIPCs are proteins with a GIPC homology 1 (GH1) domain, a central PDZ domain and a GH2 domain. This model corresponds to the GH2 domain, which mediates the interaction with myosin VI and is involved in homodimerization in the autoinhibited state.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 537152837 462 GRRDQ--SAAVVETARSSAGAQAFARGLDAVLGEFAFPDEFVVEVWAAI 508
Cdd:cd21180   17 GIRDDelAQTIVELGKDKSNPDEFAEALDESLGDFAFPDEFVFDVWGAI 65

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837   315 ETKEVEVTKTEDALGLTITDNGA--GYAFIKRIKEGSVINRiEAVCVGDSIEAINDHSIVGCRHYEVAKMLRElpKSQPF 392
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGGKDegGGVVVSSVVPGSPAAK-AGLRVGDVILEVNGTSVEGLTHLEAVDLLKK--AGGKV 77

                   ....*..
gi 537152837   393 TLRLVQP 399
Cdd:smart00228  78 TLTVLRG 84

PDZ domain of PDZ domain-containing protein GIPC3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC3, and related domains. GIPC3 (also known as C19orf64) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837 313 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPKSQPF 392
Cdd:cd23079    1 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIIDRIKAVCVGDHIEAINDQSIVGCRHYEVAKMLRELPKSQPF 80

                 ....*....
gi 537152837 393 TLRLVQPRR 401
Cdd:cd23079   81 TLRLVEPKR 89

high mobility group (HMG)-box found in high mobility group protein 20A (HMG20A) and similar proteins; HMG20A, also called HMG box-containing protein 20A, HMG domain-containing protein 1 (HMGXB1), HMG domain-containing protein HMGX1, HMGXB1, or iBRAF, is a chromatin-associated protein involved in neuronal differentiation and maturation. It is required for SNAI1-mediated epithelial to mesenchymal transition. HMG20A acts as an inhibitor of HMG20B.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837  82 KKRGWPKGKKRKKIL--PNGPKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQ 159
Cdd:cd22017    1 KRGGWSKGRKRKKPLrdSNAPKAPLTGYVRFMNERREQLRAERPDVPFPEITRMLGNEWSKLPAEEKQRYLDEAEKDKER 80

                         90       100
                 ....*....|....*....|...
gi 537152837 160 YLKELWAYQQSEAYKVCTEKIQE 182
Cdd:cd22017   81 YMKELEQYQKTEAYKLFSRKAQD 103

PDZ domain of PDZ domain-containing protein GIPC2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC2, and related domains. GIPC2 belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc2 gene have been linked to cancer. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837 311 HVRGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPKSQ 390
Cdd:cd23078    1 HVKGIKKEVNVYKSEDSLGLTITDNGVGYAFIKRIKDGSVIDSVKTICVGDHIECINGENIVGWRHYEVAKKLKELKKEE 80

                         90
                 ....*....|...
gi 537152837 391 PFTLRLVQPRRAF 403
Cdd:cd23078   81 LFTLKLIEPKKAF 93

Chromatin-associated proteins containing the HMG domain [Chromatin structure and dynamics];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837  79 EPVKKRGWPKGKKRKKIlPNGPKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQ 158
Cdd:COG5648   51 KPRKKTKSKRLVRKKKD-PNGPKRPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKEANSDRE 129

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837 159 QYLKELWAYQQSEAYKVCTEKIQEN--KIKKEDSGSGLMNTLLNGHK--GVDCDGFStfdvPIFTEEFLDQNKAREAE 232
Cdd:COG5648  130 RYQREKEEYNKKLPNKAPIGPFIENepKIRPKVEGPSPDKALVEETKiiSKAWSELD----ESKKKKYIDKYKKLKEE 203

high mobility group (HMG)-box found in Saccharomyces cerevisiae non-histone chromosomal proteins NHP6A, NHP6B and similar proteins; This subfamily includes Saccharomyces cerevisiae high-mobility-group proteins NHP6A and its closely related paralog NHP6B. NHP6A and NHP6B seem to be functionally redundant. They are DNA-binding proteins that induce severe bending of DNA and are required for DNA-binding by the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. They augment the fidelity of transcription by RNA polymerase III independently of any role in the FACT complex. They may also play essential roles in transcriptional initiation fidelity of some but not all tRNA genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837  87 PKGKKRKKILPNGPKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWA 166
Cdd:cd01390    1 KKKKGRKKKDPNAPKRGLSAYMFFSQDNREKVKEENPDATFGEVGKLLGEKWKELSEEEKAPYEEKAAKDKKRYEEEKAA 80

                 .
gi 537152837 167 Y 167
Cdd:cd01390   81 Y 81

high mobility group;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837   100 PKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAY 167
Cdd:smart00398   2 PKRPMSAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMPEY 69

high mobility group (HMG)-box found in structure-specific recognition protein 1 (SSRP1) and similar proteins; SSRP1, also called FACT complex subunit SSRP1, chromatin-specific transcription elongation factor 80 kDa subunit, facilitates chromatin transcription complex 80 kDa subunit (FACT 80 kDa subunit or FACTp80), facilitates chromatin transcription complex subunit SSRP1, recombination signal sequence recognition protein 1, or T160, is a factor that facilitates transcript elongation through nucleosomes. It is a component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication, and DNA repair.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 537152837 103 PVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAYQ 168
Cdd:cd21994    2 PMSAYMLWLNENREKIKKENPGISVTEISKKAGEIWKELDEEDKEKWEQKAEKAKERYDKAMKEYK 67

high mobility group (HMG)-box found in Saccharomyces cerevisiae non-histone protein 10 (NHP10) and similar proteins; NHP10, also called high mobility group protein 2, is probably involved in transcription regulation via its interaction with the INO80 complex, a chromatin remodeling complex.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 537152837  97 PNGPKAPVTGYVRFLNERREQIRTR----HPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAY 167
Cdd:cd22016    5 PNAPKRPANAFFLFCQEQREKVREEykeeHQEIDHHDLTKALAQAWRNLDAEDKKPYYELYEKDKERYEKEMEEY 79

second high mobility group (HMG)-box found in Saccharomyces cerevisiae mitochondrial ARS-binding factor 2 (ABF2), intrastrand cross-link recognition protein (Ixr1) and similar proteins; ABF2 is a close relative of the nuclear, chromosomal high-mobility group protein HMG1 in yeast mitochondria. It specifically binds to the autonomously replicating sequence 1 (ARS1). It might play a positive role in gene expression and replication. Ixr1, also called structure-specific recognition protein (SSRP), is a homolog of the yeast mitochondrial regulator ABF2. It binds to platinated DNA and confers sensitivity to the anticancer drug cisplatin. Both ABF2 and Ixr1 contain two HMG-box domains. This model corresponds to the second one.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 537152837  99 GPKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQY 160
Cdd:cd22012    1 PPKRPASAYFLFAKEVRPKLKEENPNEKYTDITKLISEKWRSLDESEKEPYQEEYEKALEEY 62

high mobility group (HMG)-box found in protein polybromo-1 (PB1) and similar proteins; PB1, also called BRG1-associated factor 180 (BAF180), or polybromo-1D, is a subunit of the PBAF (polybromo/Brg1-associated factor) chromatin-remodeling complex required for kinetochore localization during mitosis and the transcription of estrogen-responsive genes. It is involved in transcriptional activation and repression of select genes by chromatin remodeling. It acts as a negative regulator of cell proliferation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837 101 KAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQY 160
Cdd:cd21984    1 KRNPSGYILFSSEVRKSIKAENPDYSFGEISRLVGTEWRNLPAEKKAEYEERAQKQAEQN 60

second high mobility group (HMG)-box found in the high mobility group protein B (HMGB) family; HMGB proteins are chromatin-associated nuclear proteins that act as architectural factors in nucleoprotein structures, which regulate DNA-dependent processes including transcription. In mammals, four family members are present: HMGB1, HMGB2, HMGB3 and HMGB4. They regulate the expression of a wide range of genes through architectural remodeling of the chromatin structure. HMGB1, also called high mobility group protein 1 (HMG-1), is a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. It plays important roles in the regulation of a wide range of processes, including transcription, replication, DNA repair, and nucleosome formation, in the nucleus. It also plays multiple roles in regulating inflammation and responses to cell and tissue stress. HMGB2, also called high mobility group protein 2 (HMG-2), has been implicated in numerous cellular processes, including proliferation, differentiation, apoptosis, and tumor growth. It acts as a chromatin-associated nonhistone protein involved in transcriptional regulation and nucleic-acid-mediated innate immune responses in mammalian. It binds DNA to stabilize nucleosomes and promote transcription. HMGB3, also called high mobility group protein 2a (HMG-2a), or high mobility group protein 4 (HMG-4), is an X-linked member of HMGB family and functions as a universal sentinel for nucleic acid-mediated innate immune responses. HMGB3 has been implicated in the regulation of cellular proliferation and differentiation, as well as inflammatory response. HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation. It is a factor that regulates chromatin and expression of neuronal differentiation markers. The family also includes high mobility group protein B1 pseudogene 1 (HMGB1P1) and nuclear auto-antigen Sp-100. HMGB1P1, also called putative high mobility group protein B1-like 1 (HMGB1L1), or putative high mobility group protein 1-like 1 (HMG-1L1), is an HMG-box containing protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. Sp-100, also called nuclear dot-associated Sp100 protein, or speckled 100 kDa. It is a tumor suppressor that is a major constituent of the promyelocytic leukemia (PML) bodies, a subnuclear organelle involved in many physiological processes including cell growth, differentiation and apoptosis. Through the regulation of ETS1, Sp-100 may play a role in angiogenesis, controlling endothelial cell motility and invasion. It may also play roles in the regulation of telomeres lengthening, TP53-mediated transcription, FAS-mediated apoptosis, etc. In addition, the family includes Drosophila melanogaster high mobility group protein DSP1 (dDSP1) and similar proteins. dDSP1, also called protein dorsal switch 1, is a Drosophila HMG1 protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. It converts Dorsal and nuclear factor (NF)-kappa B from transcriptional activators to repressors. Members of the HMGB family contain two HMG-box domains. This model corresponds to the second one.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837  98 NGPKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAY 167
Cdd:cd21979    1 NAPKRPPSAFFLFCSEHRPKIKGEHPGLSIGDVAKKLGEMWNNTSAKDKQPYEKKAAKLKEKYEKDIAAY 70

GIPC-homology 2 (GH2) domain found in the GIPC family; The GIPC family includes PDZ domain-containing proteins, GIPC1 (also called GAIP C-terminus-interacting protein, RGS-GAIP-interacting protein, RGS19-interacting protein 1, RGS19IP1, synectin, tax interaction protein 2, or TIP-2), GIPC2, and GIPC3, which may act as scaffold proteins linking heterotrimeric G-proteins to seven-transmembrane-type WNT receptor or to receptor tyrosine kinases. They might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion. GIPCs are proteins with a GIPC homology 1 (GH1) domain, a central PDZ domain and a GH2 domain. This model corresponds to the GH2 domain, which mediates the interaction with myosin VI and is involved in homodimerization in the autoinhibited state.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 537152837 462 GRRDQ--SAAVVETARSSAGAQAFARGLDAVLGEFAFPDEFVVEVWAAI 508
Cdd:cd21180   17 GIRDDelAQTIVELGKDKSNPDEFAEALDESLGDFAFPDEFVFDVWGAI 65

first high mobility group (HMG)-box found in Saccharomyces cerevisiae intrastrand cross-link recognition protein (Ixr1) and similar proteins; Ixr1, also called structure-specific recognition protein (SSRP), is a homolog of the yeast mitochondrial regulator ABF2. It binds to platinated DNA and confers sensitivity to the anticancer drug cisplatin. Ixr1 contains two HMG-box domains. This model corresponds to the first one.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 537152837 100 PKAPVTGYVRFLNE-RREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAY 167
Cdd:cd22011    1 PKRPSSAYFLFSQEiRKNLKSQGSPEEKVPELSKRAAEQWRSLTLAEKQPYYDEVEVLKKQYDVEKEEY 69

high mobility group (HMG)-box found in Saccharomyces cerevisiae high mobility group protein 1 (HMO1) and similar proteins; HMO1, also called high spontaneous mutagenesis protein 2 (HSM2), is a DNA-binding protein that is probably part of the rDNA transcription apparatus. It acts synergetically with the RPA49 subunit of RNA polymerase I during rDNA transcription. It may participate in mutagenesis control.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837 100 PKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAY 167
Cdd:cd22015    1 PKKPLTPYFAFSNHVRPQLKAERPKASPTEIAEEISERWANLSDEEKQLWEDKYEEEMKEYQKALEAY 68

HMG-box domain; This short 71 residue domain is an HMG-box domain. HMG-box domains mediate re-modelling of chromatin-structure. Mammalian HMG-box proteins are of two types: those that are non-sequence-specific DNA-binding proteins with two HMG-box domains and a long highly acidic C-tail; and a diverse group of sequence-specific transcription factor-proteins with either a single HMG-box or up to six copies, and no acidic C-tail.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 537152837   97 PNGPKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKE 163
Cdd:pfam09011   1 PNKPKRARNAYAFFVQEMIPEHKRQNPVIGFAEVSKLCSERWKNLSEEEKEKYEEMAKEDKNRYDRE 67

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 537152837 318 EVEVTKTEDA-LGLTIT--DNGAGYAFIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPKS 389
Cdd:cd00136    1 TVTLEKDPGGgLGFSIRggKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGE 75

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 7 (SOX7) and similar proteins; SOX-7 is an endothelial-associated transcription factor that acts as a tumor suppressor in a number of cancer types. It binds the DNA sequence 5'-AACAAT-3'. SOX-7 belongs to the group F of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837 101 KAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAYQ 168
Cdd:cd22046   13 RRPMNAFMVWAKDERKRLAVQNPDLHNAELSKMLGKSWKALTPSQKRPYVEEAERLRVQHMQDYPNYK 80

high mobility group (HMG)-box found in Arabidopsis thaliana high mobility group B protein 9 (HMGB9) and similar proteins; This subfamily contains a group of Arabidopsis thaliana HMGB family proteins, including HMGB9, 10, 11, and 15. They are DNA-binding proteins containing both HMG-box and AT-rich interaction domains. They bind preferentially to DNA with A/T-rich content. HMGB9 is required for karyogamy during female gametophyte development, when the two polar nuclei fuse to form the diploid central cell nucleus. Members of this subfamily have only one HMG-box domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837 100 PKAPVTGYVRFLNERREQIRTRHPDLPfPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAY 167
Cdd:cd22009    1 PKPNRSGYNFFFAEQHARLKALYPGKD-REISKMIGEMWSNLTEEEKEVYQDKGVEDKERYKREMEEY 67

high mobility group (HMG)-box found in HMG box-containing protein 2 (HBP2) and similar proteins; HBP2, also called HMG box transcription factor BBX, or Bobby sox homolog, is a transcription factor that is necessary for cell cycle progression from the G1 to S phase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 537152837 101 KAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKE 163
Cdd:cd21989    1 RRPMNAFLLFCKRHRSLVRERHPRLDNRGITKILGDWWAVLDPDEKQKYTDLAKQYKEAFMKA 63

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837   315 ETKEVEVTKTEDALGLTITDNGA--GYAFIKRIKEGSVINRiEAVCVGDSIEAINDHSIVGCRHYEVAKMLRElpKSQPF 392
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGGKDegGGVVVSSVVPGSPAAK-AGLRVGDVILEVNGTSVEGLTHLEAVDLLKK--AGGKV 77

                   ....*..
gi 537152837   393 TLRLVQP 399
Cdd:smart00228  78 TLTVLRG 84

first high mobility group (HMG)-box found in the high mobility group protein B (HMGB) family; HMGB proteins are chromatin-associated nuclear proteins that act as architectural factors in nucleoprotein structures, which regulate DNA-dependent processes including transcription. In mammals, four family members are present: HMGB1, HMGB2, HMGB3 and HMGB4. They regulate the expression of a wide range of genes through architectural remodeling of the chromatin structure. HMGB1, also called high mobility group protein 1 (HMG-1), is a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. It plays important roles in the regulation of a wide range of processes, including transcription, replication, DNA repair, and nucleosome formation, in the nucleus. It also plays multiple roles in regulating inflammation and responses to cell and tissue stress. HMGB2, also called high mobility group protein 2 (HMG-2), has been implicated in numerous cellular processes, including proliferation, differentiation, apoptosis, and tumor growth. It acts as a chromatin-associated nonhistone protein involved in transcriptional regulation and nucleic-acid-mediated innate immune responses in mammalian cells. It binds DNA to stabilize nucleosomes and promote transcription. HMGB3, also called high mobility group protein 2a (HMG-2a), or high mobility group protein 4 (HMG-4), is an X-linked member of the HMGB family that functions as a universal sentinel for nucleic acid-mediated innate immune responses. HMGB3 has been implicated in the regulation of cellular proliferation and differentiation, as well as inflammatory responses. HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation. It is a factor that regulates chromatin and expression of neuronal differentiation markers. This family also includes high mobility group protein B1 pseudogene 1 (HMGB1P1) and nuclear auto-antigen Sp-100. HMGB1P1, also called putative high mobility group protein B1-like 1 (HMGB1L1), or putative high mobility group protein 1-like 1 (HMG-1L1), is an HMG-box containing protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. Sp-100, also called nuclear dot-associated Sp100 protein, or speckled 100 kDa, is a tumor suppressor that is a major constituent of promyelocytic leukemia (PML) bodies, a subnuclear organelle involved in many physiological processes including cell growth, differentiation and apoptosis. Through the regulation of ETS1, Sp-100 may play a role in angiogenesis, controlling endothelial cell motility and invasion. It may also play roles in the regulation of telomere lengthening, TP53-mediated transcription, FAS-mediated apoptosis, etc. In addition, the family includes Drosophila melanogaster high mobility group protein DSP1 (dDSP1) and similar proteins. dDSP1, also called protein dorsal switch 1, binds preferentially to single-stranded DNA and unwinds double-stranded DNA. It converts Dorsal and nuclear factor (NF)-kappa B from transcriptional activators to repressors. Members of the HMGB family contain two HMG-box domains. This model corresponds to the first one.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 537152837 100 PKAPVTGYVRFLNERREQIRTRHPDLP--FPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKEL 164
Cdd:cd21978    2 PRGKMSSYAFFVQTCREEHKKKHPNESvnFSEFSKKCSERWKTMSAKEKKKFEDMAKKDKARYEREM 68

high mobility group (HMG)-box found in group F SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxF transcription factors includes three members: Sox7, Sox17, and Sox18. They regulate endothelial cell fate as well as development and differentiation of the developing heart, blood cells, and lymphatic vessels.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 537152837 103 PVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKE 163
Cdd:cd22032    5 PMNAFMVWAKDERKRLADENPDLHNAELSKMLGKKWKSLSLAEKRPFVEEAERLRVQHMQD 65

high mobility group (HMG)-box found in group C SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxC transcription factors includes three members: SOX4, SOX11 and SOX12. They play key roles, often in redundancy, in multiple developmental pathways, including neurogenesis and skeletogenesis. SOX-4 is a transcriptional activator that promotes neuronal differentiation both in the adult and embryonic neural progenitors. It binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif. SOX-4 is abnormally expressed in various cancers. SOX-11 is a neural transcriptional factor involved in precursor survival, neuronal fate determination, migration and morphogenesis. SOX-12, also called SOX-22, is a transcription factor essential for embryonic development and cell fate determination. It binds to the sequence 5'-AACAAT-3'.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 537152837 113 ERReQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKE 163
Cdd:cd22029   16 ERR-KIMEQQPDMHNAEISKRLGKRWKLLSDSEKIPFIEEAERLRLLHMQE 65

high mobility group (HMG)-box found in group B SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxB transcription factors play critical roles in the regulation of neurogenesis. They can be divided into two main subgroups, SoxB1 (Sox-1/Sox-2/Sox-3) and SoxB2 (SOX-14/SOX-21). SoxB1 proteins suppress neurogenesis by maintaining neural cells in an undifferentiated state. SoxB2 proteins may have the opposite activity and promote neuronal differentiation. SOX-1 is involved in the regulation of embryonic development and cell fate determination. It also acts as a tumor suppressor that plays an anti-tumorigenicity role in different cells and its expression is inhibited in a variety of cancers. SOX-2 plays an important role in various phases of embryonic development, including cell fate and differentiation. Its overexpression and gene amplification may be associated with tumor aggression and metastasis in various cancer types, including breast, prostate, lung, ovarian and colon cancer. SOX-3 is required during the formation of the hypothalamic-pituitary axis. It plays a role in both normal neural development and carcinogenesis. SOX-14, also called SOX-28, acts as a negative regulator of transcription. It is mainly involved in the regulation of neural development. It can also promote proliferation and invasion capacity of cervical cancer cells by activating the Wnt/beta-catenin pathway. SOX-21, also called SOX-A, or SOX-25, promotes the progression of vertebrate neurogenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 537152837 101 KAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKE 163
Cdd:cd01388    4 KRPMNAFMVWSRGQRRKMAQENPKMHNSEISKRLGAEWKLLSEAEKRPFIDEAKRLRALHMKE 66

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 18 (SOX18) and similar proteins; SOX-18 is a transcription factor involved in the development of cardiovascular and lymphatic vessels during embryonic development. It binds to the consensus sequence 5'-AACAAAG-3' and is able to trans-activate transcription via this site. SOX-18 belongs to the group F of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 537152837 101 KAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKE 163
Cdd:cd22048    5 RRPMNAFMVWAKDERKRLAQQNPDLHNAVLSKMLGQSWKSLSAAEKRPFVEEAERLRVQHLQD 67

high mobility group (HMG)-box found in WD repeat and HMG-box DNA-binding protein 1 (WDHD1) and similar proteins; WDHD1, also called acidic nucleoplasmic DNA-binding protein 1 (And-1), acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 537152837 100 PKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYldeAEKEKQQYLKE 163
Cdd:cd21993    2 NKKKKSGFQLWLEENRSSIEEENPELSEAEIIKLAMQRFRALPKEEKQKW---NEKAKGDSDEE 62

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837 318 EVEVTKTEDALGLTItDNGAGYA------FIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPkSQP 391
Cdd:cd06763    3 TVELEKGSAGLGFSL-EGGKGSPlgdrplTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIKSLP-EGP 80

                 ...
gi 537152837 392 FTL 394
Cdd:cd06763   81 VTL 83

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 537152837 318 EVEVTKTED-ALGLTI--TDNGAGYAFIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRE 385
Cdd:cd06734    3 DVTLTRRENeGFGFVIisSVNKKSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKD 73

PDZ domain of connector enhancer of kinase suppressor of ras 1 (CNK1), CNK2, CNK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CNK1 (also known as connector enhancer of KSR 1 (CNKSR1), CNK homolog protein 1, connector enhancer of KSR-like), CNK2 (also known as CNKSR2, CNK homolog protein 2), and CNK3 (also known as CNKSR3, CNK homolog protein 3, CNKSR family member 3, maguin-like). CNK proteins modulate Ras-mediated signaling, acting downstream of Ras as a scaffold for the Raf/MEK/ERK kinase cascade. They also modulate signaling mediated via Rho family small GTPases, through interactions with various guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and modulate the insulin signaling pathway through interactions with the Arf guanine nucleotide exchange factors. CNK proteins also regulate cell proliferation and migration by acting as scaffolds for the PI3K/Akt and JNK signaling cascades. CNK2 plays a role in the molecular processes that govern morphology of the postsynaptic density (PSD), and influences subcellular localization of the regulatory NCK-interacting kinase TNIK. TNIK binds a region of CNK2 including the PDZ and the DUF domain; this region also binds the kinase MINK1. CNK2 may also influence the membrane localization of MINK1. CNK3 plays a part in transepithelial sodium transport; it coordinates assembly of an epithelial sodium channel (ENaC)-regulatory complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This CNK1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 537152837 323 KTEDALGLTITDNGAGYAFIKRIKEGSVINRIEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPKSQPFTLR 395
Cdd:cd06748    9 KPEEGLGLEIKSTYNGLHVITGTKENSPADRCGKIHAGDEVIQVNYQTVVGWQLKNLVRALREDPHGVTLTLK 81

high mobility group (HMG)-box found in group D SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxD transcription factors includes three members, Sox5, Sox6, and Sox13. They function as important transcriptional regulators of glial development in the central nervous system. SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. This subfamily also contains SoxD transcription factor homolog EGL-13, which specifies distinct O2 and CO2 sensory neuron fates in Caenorhabditis elegans. SOX-5 plays important roles in various cancer types. It binds specifically to the DNA sequence 5'-AACAAT-3'. SOX-6 plays a key role in cell proliferation, differentiation, and cell fate determination, as well as neurogenesis and skeleton formation. It is a tumor suppressor and downregulated in various cancers. SOX-6 binds specifically to the DNA sequence 5'-AACAAT-3'. SOX-13, also called Islet cell antigen 12 (ICA12), or type 1 diabetes auto-antigen ICA12, modulates T cell specification and is an autoimmune antigen. It binds to the sequence 5'-AACAAT-3'.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837 101 KAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAYQ 168
Cdd:cd22030    3 KRPMNAFMVWAKDERRKILQAFPDMHNSNISKILGSRWKSMSNQEKQPYYEEQARLSKQHLEKYPDYK 70

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 12 (SOX12) and similar proteins; SOX-12, also called SOX-22, is a transcription factor essential for embryonic development and cell fate determination. It binds to the sequence 5'-AACAAT-3'. SOX-12 belongs to the group C of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 537152837 101 KAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPSEKQRYLDEAEKEKQQYLKELWAYQ 168
Cdd:cd22038   13 KRPMNAFMVWSQIERRKIMEQWPDMHNAEISKRLGRRWKLLQDYEKIPFIKEAERLRLKHMADYPDYK 80

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 537152837 314 GETKEVEVTKTEDALGLTIT--DN---GAGYAFIKRI-KEGSVIN--RIEAvcvGDSIEAINDHSIVGCRHYEVAKMLRE 385
Cdd:cd23058    3 GKKLHIQLKKGPEGLGFSITsrDNptgGSGPIYIKNIlPKGAAIQdgRLKA---GDRLLEVNGVDVTGKTQEEVVSLLRS 79

                 ....*....
gi 537152837 386 LPKSQPFTL 394
Cdd:cd23058   80 TKLGGTVSL 88