high mobility group (HMG)-box found in high mobility group protein 20B (HMG20B) and similar proteins; HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2 (HMGXB2), HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  88 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKMCTE 167
Cdd:cd22018     1 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQQSEAYKMCTE 80

                  ....*
gi 1495271822 168 KIQEK 172
Cdd:cd22018    81 KIQEK 85

GIPC homology 2 (GH2) domain-like family; The GIPC (GAIP C-terminus-interacting protein) family of proteins mediate endocytosis by tethering cargo proteins to the motor myosin VI. This model represents the C-terminal GIPC homology 2 or GH2 domain (plus the linker to the PDZ domain located N-terminally of GH2), which mediates the interaction with myosin VI and is involved in homodimerization in the autoinhibited state. The family also includes DEAH box protein 8 (DHX8) and similar proteins. DHX8 (a human homolog of yeast Prp22), also called RNA helicase HRH1, is an ATP-dependent RNA helicase involved in pre-mRNA splicing as a component of the spliceosome. It facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome. DHX8 contains a GH2-like domain at the N-terminus, which shows high sequence similarity with the GH2 domain found in GIPC proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1495271822 497 ASTMVEAAKASPSVGQLAQGLDSVLGEFAFPPEFIAEVWAAV 538
Cdd:cd21180    24 AQTIVELGKDKSNPDEFAEALDESLGDFAFPDEFVFDVWGAI 65

high mobility group (HMG)-box found in high mobility group protein 20B (HMG20B) and similar proteins; HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2 (HMGXB2), HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  88 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKMCTE 167
Cdd:cd22018     1 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQQSEAYKMCTE 80

                  ....*
gi 1495271822 168 KIQEK 172
Cdd:cd22018    81 KIQEK 85

HMG (high mobility group) box;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1495271822  89 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 156
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAEKEKARYEKEHPEY 68

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  62 GEKPEEEPVKKRGWPKGKKRKKIlPNGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDE 141
Cdd:COG5648    45 LQQLLTKPRKKTKSKRLVRKKKD-PNGPKRPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKE 123

                          90       100
                  ....*....|....*....|..
gi 1495271822 142 AEREKQQYMKELREYQQSEAYK 163
Cdd:COG5648   124 ANSDRERYQREKEEYNKKLPNK 145

high mobility group protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  77 KGKKRKKILPNGPKAPVTGYVRFLNERREQIRTQHPDLP--FPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELR 154
Cdd:PTZ00199   11 RKNKRKKKDPNAPKRALSAYMFFAKEKRAEIIAENPELAkdVAAVGKMVGEAWNKLSEEEKAPYEKKAQEDKVRYEKEKA 90

                  ....
gi 1495271822 155 EYQQ 158
Cdd:PTZ00199   91 EYAK 94

PDZ domain; PDZ domains are found in diverse signaling proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1495271822 421 LGLTI---TDNGAGYAFIKRIKEGSIINRlQTVCVGDSIEAINDHTIVGCRHYEVARMLRE 478
Cdd:pfam00595  12 LGFSLkggSDQGDPGIFVSEVLPGGAAEA-GGLKVGDRILSINGQDVENMTHEEAVLALKG 71

high mobility group (HMG)-box found in high mobility group protein 20B (HMG20B) and similar proteins; HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2 (HMGXB2), HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  88 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKMCTE 167
Cdd:cd22018     1 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQQSEAYKMCTE 80

                  ....*
gi 1495271822 168 KIQEK 172
Cdd:cd22018    81 KIQEK 85

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins 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 Gipc1 and Gipc2 genes have been linked to cancer, while 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 GIPC family 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 1495271822 406 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIINRLQTVCVGDSIEAINDHTIVGCRHYEVARMLRELPRAQPF 485
Cdd:cd06707     1 KGQPKEIEVTKSEDALGLTITDNGAGYAFIKRIKEGSIMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKEIPIGETF 80

                  ....*....
gi 1495271822 486 TLRLVQPKK 494
Cdd:cd06707    81 TLRLVEPKK 89

high mobility group (HMG)-box found in the high mobility group protein 20 (HMG20) subfamily; The HMG20 subfamily includes HMG20A and HMG20B. HMG20A, also called HMG box-containing protein 20A, HMG domain-containing protein 1, 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. HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2, HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex. Both HMG20A and HMG20B contain one HMG-box.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1495271822  89 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKM 164
Cdd:cd21980     2 PKAPLTGYVRFLNERREKLRAENPDLSFPEITKILGAEWSSLSAEEKQKYLDEAEKDKERYVKELEAYQQTEAYKA 77

PDZ domain of PDZ domain-containing protein GIPC1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC1, and related domains. GIPC1 (also known as GIPC, GAIP/RGS19-interacting protein or Tax-interacting protein 2) 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. GIPC1 functions as an adaptor molecule for loading PDZ-target cargoes on the MYO6 motor protein. The GIPC1 PDZ domain interacts with a variety of ligands, such as RGS19, NRP1, GLUT1, SEMA4C, SDC4 and IGF1R. 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 GIPC1 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 1495271822 404 HVRGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIINRLQTVCVGDSIEAINDHTIVGCRHYEVARMLRELPRAQ 483
Cdd:cd23077     1 HVKGQRKEVEVFKSEDALGLTITDNGAGYAFIKRIKEGSVIDRIQLISVGDMIEAINGQSLLGCRHYEVARLLKELPRGR 80

                          90
                  ....*....|...
gi 1495271822 484 PFTLRLVQPKKAF 496
Cdd:cd23077    81 TFTLKLTEPRKAF 93

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 1495271822  76 PKGKKRKKILPNGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELRE 155
Cdd:cd01390     1 KKKKGRKKKDPNAPKRGLSAYMFFSQDNREKVKEENPDATFGEVGKLLGEKWKELSEEEKAPYEEKAAKDKKRYEEEKAA 80

                  .
gi 1495271822 156 Y 156
Cdd:cd01390    81 Y 81

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  62 GEKPEEEPVKKRGWPKGKKRKKIlPNGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDE 141
Cdd:COG5648    45 LQQLLTKPRKKTKSKRLVRKKKD-PNGPKRPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKE 123

                          90       100
                  ....*....|....*....|..
gi 1495271822 142 AEREKQQYMKELREYQQSEAYK 163
Cdd:COG5648   124 ANSDRERYQREKEEYNKKLPNK 145

high mobility group (HMG)-box found in SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1) and similar proteins; SMARCE1, also called BRG1-associated factor 57 (BAF57), is a ubiquitously expressed protein involved in transcriptional activation and repression of select genes by chromatin remodeling. It is a component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. SMARCE1 has a single HMG domain that displays non-specific DNA-binding characteristics. It also contains a kinesin-like coiled-coil (KLCC) domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1495271822  86 PNGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 157
Cdd:cd21983     2 PKPPEKPLMPYMRYSRKVWDQVKASNPDLKLWEIGKIIGQMWRELSDEEKQEYIEEYEAEKVEYEEQMKAYH 73

high mobility group (HMG)-box found in Arabidopsis thaliana FACT complex subunit SSRP1 and similar proteins; SSRP1, also called facilitates chromatin transcription complex subunit SSRP1, high mobility group B protein 8, nucleosome/chromatin assembly factor group D 08 (or D 8), protein NUCLEAR FUSION DEFECTIVE 8, or recombination signal sequence recognition protein 1, 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. SSRP1 may bind specifically to double-stranded DNA. It is required for karyogamy during female gametophyte development, when the two polar nuclei fuse to form the diploid central cell nucleus. SSRP1 contains only one HMG-box domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1495271822  81 RKKILPNGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 157
Cdd:cd22013     1 KKKKDPNAPKRALSGFMFFSLMERENLKKEKPGISFGEVGKVLGEKWKNMSADDKAPYEAKAQVDKERYKKEMSGYK 77

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 1495271822  86 PNGPKAPVTGYVRFLNERREQIRT----QHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 156
Cdd:cd22016     5 PNAPKRPANAFFLFCQEQREKVREeykeEHQEIDHHDLTKALAQAWRNLDAEDKKPYYELYEKDKERYEKEMEEY 79

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 1495271822 497 ASTMVEAAKASPSVGQLAQGLDSVLGEFAFPPEFIAEVWAAV 538
Cdd:cd21180    24 AQTIVELGKDKSNPDEFAEALDESLGDFAFPDEFVFDVWGAI 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 1495271822  89 PKAPVTGYVRFLNERREQIRTQ-HPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 156
Cdd:cd22011     1 PKRPSSAYFLFSQEIRKNLKSQgSPEEKVPELSKRAAEQWRSLTLAEKQPYYDEVEVLKKQYDVEKEEY 69

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 1495271822  90 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQY 149
Cdd:cd21984     1 KRNPSGYILFSSEVRKSIKAENPDYSFGEISRLVGTEWRNLPAEKKAEYEERAQKQAEQN 60

high mobility group (HMG)-box found in sex-determining region Y (SRY)-box (SOX) family transcription factors; The SOX gene family of transcription factors are characterized by the evolutionarily conserved SRY-type HMG box, which is a DNA binding domain that binds the minor groove of DNA on a common consensus site, (A/T)(A/T)CAA(A/T)G but with different levels of efficiency. Members include SRY and its homologs identified in mammals that can be subdivided into 8 groups (A, B1, B2, C, D, E, F, G, H). They are involved in embryonic development, regulating processes such as cell differentiation, maintenance of stemness, sex determination, and development of the central nervous, haematopoietic and other organ systems. The SOX gene family has a crucial role in carcinogenesis and cancer progression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1495271822 102 ERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKE 152
Cdd:cd22004    15 QERKKIAKQNPKLHNSEISKILGKEWKKLTEEEKRPYVEEAERLREEHKKE 65

high mobility group protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  77 KGKKRKKILPNGPKAPVTGYVRFLNERREQIRTQHPDLP--FPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELR 154
Cdd:PTZ00199   11 RKNKRKKKDPNAPKRALSAYMFFAKEKRAEIIAENPELAkdVAAVGKMVGEAWNKLSEEEKAPYEKKAQEDKVRYEKEKA 90

                  ....
gi 1495271822 155 EYQQ 158
Cdd:PTZ00199   91 EYAK 94

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 1495271822  87 NGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 156
Cdd:cd21979     1 NAPKRPPSAFFLFCSEHRPKIKGEHPGLSIGDVAKKLGEMWNNTSAKDKQPYEKKAAKLKEKYEKDIAAY 70

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 1495271822  89 PKAPVTGYVRFLNERREQIRTQHPDLPfPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 156
Cdd:cd22009     1 PKPNRSGYNFFFAEQHARLKALYPGKD-REISKMIGEMWSNLTEEEKEVYQDKGVEDKERYKREMEEY 67

first high mobility group (HMG)-box found in Arabidopsis thaliana high mobility group B protein 6 (HMGB6) and similar proteins; HMGB6, also called nucleosome/chromatin assembly factor group D 06 (or D 6), WRKY transcription factor 53 (WRKY53), or WRKY DNA-binding protein 53, is a master regulator of age-induced leaf senescence. It acts in a complex transcription factor signaling network regulating senescence specific gene expression; hydrogen peroxide might be involved in signal transduction. The subfamily also includes Arabidopsis thaliana HMGB13 (also known as nucleosome/chromatin assembly factor group D 13). Both HMGB6 and HMGB13 contain three HMG-box domains. This model corresponds to the first one.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1495271822  90 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 156
Cdd:cd22006     1 KKPKTAYFLWCKDQREEVKKENPNADFSEVSKILGAKWKNLSEEEKKPYEEKYKEEKEKYLKVVGEE 67

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1495271822  86 PNGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 156
Cdd:pfam09011   1 PNKPKRARNAYAFFVQEMIPEHKRQNPVIGFAEVSKLCSERWKNLSEEEKEKYEEMAKEDKNRYDREMGTY 71

high mobility group (HMG)-box found in Saccharomyces cerevisiae repressor ROX1 and similar proteins; This family includes class I members of the HMG-box superfamily of DNA-binding proteins, including Saccharomyces cerevisiae repressor ROX1, Schizosaccharomyces pombe mating-type M-specific polypeptide Mc (mat-Mc), Schizosaccharomyces pombe transcription factor ste11, Podospora anserina MAT+ sexual cell fertilization-promoting factor (FPR1), Podospora anserina sporulation minus regulator 2 (SMR2) and Candida albicans repressor of filamentous growth 1 (RFG1). These proteins contain a single HMG box, and bind the minor groove of DNA in a highly sequence-specific manner. ROX1, also called heme-dependent repression factor, or hypoxic function repressor, is a transcription factor that represses the expression of HEM13, COX5B, ANB1, CYC7 or AAC3. It binds to the DNA sequence 5'-RRRTAACAAGAG-3'. mat-Mc belongs to the mating type protein family, which contains sequence specific DNA-binding proteins that act as master switches in yeast differentiation by controlling gene expression in a cell type-specific fashion. mat-Mc is a positive regulator of MFM genes and is required for conjugation and efficient meiosis. Its HMG box recognizes the DNA sequence 5'-AACAAAG-3'. Ste11 is a key transcription factor for sexual development. It activates the transcription of the matp, matm, mei2, mfm, ste6 and rgs1 genes. It binds specifically to a DNA fragment carrying a 10-base motif 5'-TTCTTTGTTY-3'. FPR1 controls fertilization, probably by determining the mating type. SMR2 is a transcription factor that is required for post-fertilization events. It is required for the developmental events that occur in the female organ after fertilization. RFG1 is a transcription regulator that functions in both the positive and negative regulation of filamentous growth, depending upon environmental conditions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1495271822  99 FLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKE 152
Cdd:cd01389    11 FRKEKHKQLRAQNPGLTNSEISKIIGKMWKNLSEEEKEPYKELAEEEKEEHKLK 64

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 1495271822 102 ERReQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 157
Cdd:cd22029    16 ERR-KIMEQQPDMHNAEISKRLGKRWKLLSDSEKIPFIEEAERLRLLHMQEYPDYK 70

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822 411 EVEVTKTEDA-LGLTIT--DNGAGYAFIKRIKEGSIINRLQTVCVGDSIEAINDHTIVGCRHYEVARMLRELPRaqpfTL 487
Cdd:cd00136     1 TVTLEKDPGGgLGFSIRggKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGG----EV 76

                  ...
gi 1495271822 488 RLV 490
Cdd:cd00136    77 TLT 79

high mobility group (HMG)-box found in Caenorhabditis elegans protein egg laying defective 13 (EGL-13) and similar proteins; EGL-13 may act as a transcription factor that is required for uterine cell fate decisions in Caenorhabditis elegans. It controls genes required for the specification and differentiation of O(2) and CO(2)-sensing neurons and for maintaining URX sensory neuronal cell fate.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1495271822  90 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 157
Cdd:cd22042     4 KRPMNAFMVWAKDERRKILKACPDMHNSNISKILGAKWKAMSNAEKQPYYEEQSRLSKLHMEKHPDYR 71

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 1495271822  90 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 157
Cdd:cd22048     5 RRPMNAFMVWAKDERKRLAQQNPDLHNAVLSKMLGQSWKSLSAAEKRPFVEEAERLRVQHLQDHPNYK 72

high mobility group (HMG)-box found in Arabidopsis thaliana high mobility group B protein 1 (HMGB1) and similar proteins; This subfamily contains a group of Arabidopsis thaliana HMGB family proteins, including HMGB1, 2, 3, 4, 5, 7, 12 and 14. They bind preferentially to double-stranded DNA. HMGB1 modulates general plant growth and stress tolerance and confers sensitivity to salt and genotoxic (methyl methanesulfonate, MMS) stresses. HMGB2 and HMGB5 confer sensitivity to salt and drought stresses. HMGB7 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 contain only one HMG-box domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  90 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQY 149
Cdd:cd22005     1 KRPPTAFFLFLADFRKTYKKKNPDKSVKAVGKAAGEKWKSMSDEEKAPYVEKAEKEKAEY 60

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 1495271822  90 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKE 152
Cdd:cd21989     1 RRPMNAFLLFCKRHRSLVRERHPRLDNRGITKILGDWWAVLDPDEKQKYTDLAKQYKEAFMKA 63

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 1495271822  90 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 157
Cdd:cd22030     3 KRPMNAFMVWAKDERRKILQAFPDMHNSNISKILGSRWKSMSNQEKQPYYEEQARLSKQHLEKYPDYK 70

high mobility group (HMG)-box found in basic helix-loop-helix and HMG box domain-containing protein 1 (BHMG1) and similar proteins; BHMG1 is an uncharacterized HMG-box containing protein that contains a degenerate basic motif not likely to bind DNA.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822  89 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQ 148
Cdd:cd21977     1 KKKWVNGFIMFCRLNRKNYIDKHPGLASTELTKELGQLWRELSAEEKKPYCVRARELSQL 60

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 1495271822 416 KTEDALGLTITDNGAGYAFIKRIKEGSIINRLQTVCVGDSIEAINDHTIVGCRHYEVARMLRELPRAQPFTLR 488
Cdd:cd06748     9 KPEEGLGLEIKSTYNGLHVITGTKENSPADRCGKIHAGDEVIQVNYQTVVGWQLKNLVRALREDPHGVTLTLK 81

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. 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 MPP6-MPP2-like family 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1495271822 417 TEDALGLTITDNGAGYAFIKRIKEGSIINRLQTVCVGDSIEAINDHTIVGCRHYEVARMLREL 479
Cdd:cd10831     9 TDEPMGITLKMNEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREA 71

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 30 (SOX30) and similar proteins; SOX-30 is a crucial transcription factor that controls the transition from a late meiotic to a post-meiotic gene expression program and subsequent round spermatid development. It specially prevents Wnt-signaling to suppress metastasis. SOX-30 binds to the DNA sequence 5'-ACAAT-3' and shows a preference for guanine residues surrounding this core motif. SOX-30 is the only member of the group H of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1495271822 104 REQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKE 152
Cdd:cd22033    17 RPALAKANPNANNADISVQLGEEWNKLTEEQKKPYYDEAQKLKEQHRKE 65

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 1495271822 411 EVEVTKTEDALGLTItDNGAGYA------FIKRIKEGSIINRLQTVCVGDSIEAINDHTIVGCRHYEVARMLRELPRAqP 484
Cdd:cd06763     3 TVELEKGSAGLGFSL-EGGKGSPlgdrplTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIKSLPEG-P 80

                  ...
gi 1495271822 485 FTL 487
Cdd:cd06763    81 VTL 83

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. 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 GRIP family PDZ3 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1495271822 412 VEVTKTE-DALGLTITD---NGAGYAFIKRIKEGSIINRLQTVCVGDSIEAINDHTIVGCRHYEVARMLR 477
Cdd:cd06684     5 VEIEKTPgSSLGITLSTsthRNKQVIVIDSIKPASIADRCGALHVGDHILSIDGTSVEHCSLAEATQLLA 74

second high mobility group (HMG)-box found in upstream-binding factor 1 (UBF1) and similar proteins; UBF1, also called UBTF, nucleolar transcription factor 1, or auto-antigen NOR-90, is a nucleolar transcription factor that recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element. UBF1 contains six HMG-box domains. This model corresponds to the second one.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1495271822  89 PKAPVTGYVRFLNERREQIRTQHPDLPfpEITKMLGAEWSklQLSEKQR--YLDEAEREKQQYMKELREYQQS 159
Cdd:cd21999     1 PKKPKTPFQLFYNKELKKLEPGTPDKK--ELKEKLREKWK--QMSDKKKlkWINKALEDEKRYEEELKEYKKE 69