C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  698 AQVQIGLRYDRSSSSFVIIVVQLRNLHAFSVPFGSRVYFRVAVLPSSVDISCLFRTKVHPAMETILFNEIFRVAISQEAL 777
Cdd:cd08680     1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 558195210  778 QQKTLRVDVCTVNKTRREECLAGTQLSLADLSLSNETNTLWYNL 821
Cdd:cd08680    81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                           10        20        30
                   ....*....|....*....|....*....|
gi 558195210    59 LPWGWEAAYDPQIGVYYIDHINKTTQIEDP 88
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

F-type ATP synthase, membrane subunit b; Membrane subunit b is a component of the Fo complex of FoF1-ATP synthase. The F-type ATP synthases (FoF1-ATPase) consist of two structural domains: the F1 (assembly factor one) complex containing the soluble catalytic core, and the Fo (oligomycin sensitive factor) complex containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. F1 is composed of alpha (or A), beta (B), gamma (C), delta (D) and epsilon (E) subunits with a stoichiometry of 3:3:1:1:1, while Fo consists of the three subunits a, b, and c (1:2:10-14). An oligomeric ring of 10-14 c subunits (c-ring) make up the Fo rotor. The flux of protons through the ATPase channel (Fo) drives the rotation of the c-ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the c-ring of Fo. The F-ATP synthases are primarily found in the inner membranes of eukaryotic mitochondria, in the thylakoid membranes of chloroplasts or in the plasma membranes of bacteria. The F-ATP synthases are the primary producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts). Alternatively, under conditions of low driving force, ATP synthases function as ATPases, thus generating a transmembrane proton or Na(+) gradient at the expense of energy derived from ATP hydrolysis. This group also includes F-ATP synthase that has also been found in the archaea Candidatus Methanoperedens.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210 1080 RQNRLNDELQALRDLKQKLEEMKARGETDLPQcvLEDERfQKLLKQAEKQAEQSKEEQKQ--GLSAEKLMRKASKDVCRL 1157
Cdd:cd06503    31 REEKIAESLEEAEKAKEEAEELLAEYEEKLAE--ARAEA-QEIIEEARKEAEKIKEEILAeaKEEAERILEQAKAEIEQE 107

                  ...
gi 558195210 1158 REQ 1160
Cdd:cd06503   108 KEK 110

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  698 AQVQIGLRYDRSSSSFVIIVVQLRNLHAFSVPFGSRVYFRVAVLPSSVDISCLFRTKVHPAMETILFNEIFRVAISQEAL 777
Cdd:cd08680     1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 558195210  778 QQKTLRVDVCTVNKTRREECLAGTQLSLADLSLSNETNTLWYNL 821
Cdd:cd08680    81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                            10        20        30
                    ....*....|....*....|....*....|...
gi 558195210     11 PLPDGWEEARDYDGKVFYIDHNTKQTSWIDPRD 43
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                           10        20        30
                   ....*....|....*....|....*....|
gi 558195210    59 LPWGWEAAYDPQIGVYYIDHINKTTQIEDP 88
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   164 LKAEISTTRLRVKKLKRELFHMKQELLYKEQGFETLQQiDQKMSGGQSGYELSEAKAILSELKSIRKAISSGEREKQDLM 243
Cdd:TIGR02169  686 LKRELSSLQSELRRIENRLDELSQELSDASRKIGEIEK-EIEQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELE 764

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   244 QSLAKLRERFH-LDQTVGISEPDLRSSSV-NSQLSLSRQTLDAGSQTDISGDIGVKSRSNLAEKVRLSLQYEEAKRSMAN 321
Cdd:TIGR02169  765 ARIEELEEDLHkLEEALNDLEARLSHSRIpEIQAELSKLEEEVSRIEARLREIEQKLNRLTLEKEYLEKEIQELQEQRID 844

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   322 LKIELSkldsetwpgalDIEKEKLMLINEKEELLKELQFVTPRKRT-QDELEHLEAERKRLEEELLSVKSTPSQALAERL 400
Cdd:TIGR02169  845 LKEQIK-----------SIEKEIENLNGKKEELEEELEELEAALRDlESRLGDLKKERDELEAQLRELERKIEELEAQIE 913

                          250
                   ....*....|....*
gi 558195210   401 KLEERRKELVQKLEE 415
Cdd:TIGR02169  914 KKRKRLSELKAKLEA 928

F-type ATP synthase, membrane subunit b; Membrane subunit b is a component of the Fo complex of FoF1-ATP synthase. The F-type ATP synthases (FoF1-ATPase) consist of two structural domains: the F1 (assembly factor one) complex containing the soluble catalytic core, and the Fo (oligomycin sensitive factor) complex containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. F1 is composed of alpha (or A), beta (B), gamma (C), delta (D) and epsilon (E) subunits with a stoichiometry of 3:3:1:1:1, while Fo consists of the three subunits a, b, and c (1:2:10-14). An oligomeric ring of 10-14 c subunits (c-ring) make up the Fo rotor. The flux of protons through the ATPase channel (Fo) drives the rotation of the c-ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the c-ring of Fo. The F-ATP synthases are primarily found in the inner membranes of eukaryotic mitochondria, in the thylakoid membranes of chloroplasts or in the plasma membranes of bacteria. The F-ATP synthases are the primary producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts). Alternatively, under conditions of low driving force, ATP synthases function as ATPases, thus generating a transmembrane proton or Na(+) gradient at the expense of energy derived from ATP hydrolysis. This group also includes F-ATP synthase that has also been found in the archaea Candidatus Methanoperedens.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210 1080 RQNRLNDELQALRDLKQKLEEMKARGETDLPQcvLEDERfQKLLKQAEKQAEQSKEEQKQ--GLSAEKLMRKASKDVCRL 1157
Cdd:cd06503    31 REEKIAESLEEAEKAKEEAEELLAEYEEKLAE--ARAEA-QEIIEEARKEAEKIKEEILAeaKEEAERILEQAKAEIEQE 107

                  ...
gi 558195210 1158 REQ 1160
Cdd:cd06503   108 KEK 110

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  164 LKAEISTTRLRVKKLKRELFHMKQ-ELLYKEQG---FETLQQIDQKMSG-GQSGYELSEAKAILSELKSIRKAISSGERE 238
Cdd:PRK03918  167 LGEVIKEIKRRIERLEKFIKRTENiEELIKEKEkelEEVLREINEISSElPELREELEKLEKEVKELEELKEEIEELEKE 246

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  239 KQDLMQSLAKLRERFHLDQTvGISEPDLRSSSVNSQLSlsrqtldagsqtdisgdiGVKSRSNLAEK-VRLSLQYEEAKR 317
Cdd:PRK03918  247 LESLEGSKRKLEEKIRELEE-RIEELKKEIEELEEKVK------------------ELKELKEKAEEyIKLSEFYEEYLD 307

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  318 SMANLKIELSKLDS------ETWPGALDIEKEKLMLINEKEELLKELQFVTPRKRTQDELEHLEAERKRLEEELlsVKST 391
Cdd:PRK03918  308 ELREIEKRLSRLEEeingieERIKELEEKEERLEELKKKLKELEKRLEELEERHELYEEAKAKKEELERLKKRL--TGLT 385

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 558195210  392 PSQALAERLKLEERRKELVQKLEETTKLTTYLHSQLKSL 430
Cdd:PRK03918  386 PEKLEKELEELEKAKEEIEEEISKITARIGELKKEIKEL 424

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  698 AQVQIGLRYDRSSSSFVIIVVQLRNLHAFSVPFGSRVYFRVAVLPSSVDISCLFRTKVHPAMETILFNEIFRVAISQEAL 777
Cdd:cd08680     1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 558195210  778 QQKTLRVDVCTVNKTRREECLAGTQLSLADLSLSNETNTLWYNL 821
Cdd:cd08680    81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                            10        20        30
                    ....*....|....*....|....*....|...
gi 558195210     11 PLPDGWEEARDYDGKVFYIDHNTKQTSWIDPRD 43
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  698 AQVQIGLRYDRSSSSFVIIVVQLRNLHAFSVPFGSRVYFRVAVLPSSvDISCLFRTKVHPAMETILFNEIFRVAISQEAL 777
Cdd:cd04030     3 GRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDK-SKSTRRKTSVKKDNLNPVFDETFEFPVSLEEL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 558195210  778 QQKTLRVDVCTvNKT---RREECLAGTQLSLADLSLSNETnTLWYNL 821
Cdd:cd04030    82 KRRTLDVAVKN-SKSflsREKKLLGQVLIDLSDLDLSKGF-TQWYDL 126

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  699 QVQIGLRYDRSSSSFVIIVVQLRNLHAFSVPFGSRVYFRVAVLPssvDISCLFRTKVHPAMETILFNEIFRVAISQEALQ 778
Cdd:cd08387     4 ELHFSLEYDKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLP---DRSNTKQSKIHKKTLNPEFDESFVFEVPPQELP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 558195210  779 QKTLRVDVCTVNKTRREECLAGTQLSLADLSLSnETNTLW 818
Cdd:cd08387    81 KRTLEVLLYDFDQFSRDECIGVVELPLAEVDLS-EKLDLW 119

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20
                  ....*....|....*....|....*...
gi 558195210   62 GWEAAYDPQIGVYYIDHINKTTQIEDPR 89
Cdd:cd00201     3 GWEERWDPDGRVYYYNHNTKETQWEDPR 30

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  713 FVIIVVQLRNLHAFSVPFGSRVYFRVAVLPSSVdisclFRTKVHPAMETILFNEIFRVAISQEalQQKTLRVDVCTVNKT 792
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQK-----FKTKVVKNTLNPVWNETFEFPVLDP--ESDTLTVEVWDKDRF 73

                          90       100
                  ....*....|....*....|....*....
gi 558195210  793 RREECLAGTQLSLADLSLSNETNTLWYNL 821
Cdd:cd00030    74 SKDDFLGEVEIPLSELLDSGKEGELWLPL 102

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   164 LKAEISTTRLRVKKLKRELFHMKQELLYKEQGFETLQQIDQKMSGGQSGYELSEAKAILSELKSIRKAISSGEREKQDLM 243
Cdd:TIGR02169  242 IERQLASLEEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLGEEEQLRVKEKIGELEAEIASLERSIAEKERELEDAE 321

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   244 QSLAKLRERfhldqtvgisepdlrsssvnsqlsLSRQTLDAgsqTDISGDIGVKSRsnlaEKVRLSLQYEEAKRSMANLK 323
Cdd:TIGR02169  322 ERLAKLEAE------------------------IDKLLAEI---EELEREIEEERK----RRDKLTEEYAELKEELEDLR 370

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   324 IELSKLDSE--TWPGALDIEKEKL-MLINEKEELLKELQFVTPRKRTQD-ELEHLEAERKRLEEELLSVKSTPSQALAER 399
Cdd:TIGR02169  371 AELEEVDKEfaETRDELKDYREKLeKLKREINELKRELDRLQEELQRLSeELADLNAAIAGIEAKINELEEEKEDKALEI 450

                          250
                   ....*....|....*
gi 558195210   400 LKLEERRKELVQKLE 414
Cdd:TIGR02169  451 KKQEWKLEQLAADLS 465

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  704 LRYDRSSSSFVIIVVQLRNLHAFSVPFGSRV-YFRVAVLPssvDISCLFRTKV-----HPAmetilFNEIFRVAISQEAL 777
Cdd:cd08390     7 VQYDLEEEQLTVSLIKARNLPPRTKDVAHCDpFVKVCLLP---DERRSLQSKVkrktqNPN-----FDETFVFQVSFKEL 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 558195210  778 QQKTLRVDVCTVNKTRREECLAGTQLSLADLSLSnETNTLWYNLLP 823
Cdd:cd08390    79 QRRTLRLSVYDVDRFSRHCIIGHVLFPLKDLDLV-KGGVVWRDLEP 123

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  700 VQIGLRYDRSSSSFVIIVVQLRNLHAFSVPFG-SRVYFRVAVLPSSVDISCLfRTKVHPAMETILFNEIFRVAISQEALQ 778
Cdd:cd08393     4 VQFALDYDPKLRELHVHVIQCQDLAAADPKKQrSDPYVKTYLLPDKSNRGKR-KTSVKKKTLNPVFNETLRYKVEREELP 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 558195210  779 QKTLRVDVCTVNKTRREECLAGTQLSLADLSLSNETNTlWYNL 821
Cdd:cd08393    83 TRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQPT-WYPL 124

F-type ATP synthase, membrane subunit b; Membrane subunit b is a component of the Fo complex of FoF1-ATP synthase. The F-type ATP synthases (FoF1-ATPase) consist of two structural domains: the F1 (assembly factor one) complex containing the soluble catalytic core, and the Fo (oligomycin sensitive factor) complex containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. F1 is composed of alpha (or A), beta (B), gamma (C), delta (D) and epsilon (E) subunits with a stoichiometry of 3:3:1:1:1, while Fo consists of the three subunits a, b, and c (1:2:10-14). An oligomeric ring of 10-14 c subunits (c-ring) make up the Fo rotor. The flux of protons through the ATPase channel (Fo) drives the rotation of the c-ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the c-ring of Fo. The F-ATP synthases are primarily found in the inner membranes of eukaryotic mitochondria, in the thylakoid membranes of chloroplasts or in the plasma membranes of bacteria. The F-ATP synthases are the primary producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts). Alternatively, under conditions of low driving force, ATP synthases function as ATPases, thus generating a transmembrane proton or Na(+) gradient at the expense of energy derived from ATP hydrolysis. This group also includes F-ATP synthase that has also been found in the archaea Candidatus Methanoperedens.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210 1080 RQNRLNDELQALRDLKQKLEEMKARGETDLPQcvLEDERfQKLLKQAEKQAEQSKEEQKQ--GLSAEKLMRKASKDVCRL 1157
Cdd:cd06503    31 REEKIAESLEEAEKAKEEAEELLAEYEEKLAE--ARAEA-QEIIEEARKEAEKIKEEILAeaKEEAERILEQAKAEIEQE 107

                  ...
gi 558195210 1158 REQ 1160
Cdd:cd06503   108 KEK 110

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   78 HINKTTQIEDPRKQWRQEQERMlKDY--LTVAQDALSTQKELYQVKEQRLALALDEYVRLNDAYKEKSSSRTSLFSSSSS 155
Cdd:COG4717    66 PELNLKELKELEEELKEAEEKE-EEYaeLQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAELAEL 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  156 STKYDpdilkaEISTTRLRVKKLKRELFHMKQELLYKEQGFETLQQIDQKMSGGQSGYELSEAKAILSELKSIRKAISSG 235
Cdd:COG4717   145 PERLE------ELEERLEELRELEEELEELEAELAELQEELEELLEQLSLATEEELQDLAEELEELQQRLAELEEELEEA 218

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  236 EREKQDLMQSLAKLRERFHLDQTVG-ISEPDLRSSSVNSQLSLSRQTLDAGSQTDISGDIGVKSRSNLA------EKVRL 308
Cdd:COG4717   219 QEELEELEEELEQLENELEAAALEErLKEARLLLLIAAALLALLGLGGSLLSLILTIAGVLFLVLGLLAllflllAREKA 298

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  309 SLQYEEAKRSMANLKIELSKLDSETWPGALDIEKE-KLMLINEKEELLKELQFVTPRKRTQDELEHLEAERKRLEEELLS 387
Cdd:COG4717   299 SLGKEAEELQALPALEELEEEELEELLAALGLPPDlSPEELLELLDRIEELQELLREAEELEEELQLEELEQEIAALLAE 378

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 558195210  388 VKSTPSQALAERLKLEERRKELVQKLEEttkLTTYLHSQLKSLSA 432
Cdd:COG4717   379 AGVEDEEELRAALEQAEEYQELKEELEE---LEEQLEELLGELEE 420

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  700 VQIGLRYDRSSSSFVIIVVQLRNLHAFSVPFGSRVYFRVAVLPSSVDiscLFRTKVHPAMETiLFNEIFRVA-ISQEALQ 778
Cdd:cd08389     5 LDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWQVHLVLLPSKKQ---RAKTKVQRGPNP-VFNETFTFSrVEPEELN 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 558195210  779 QKTLRVDVCTVNKTRREECLAGTQLSLADLSLSNETnTLWYNLLP 823
Cdd:cd08389    81 NMALRFRLYGVERMRKERLIGEKVVPLSQLNLEGET-TVWLTLEP 124

Uncharacterized conserved protein, contains TOPRIM domain, potential nuclease [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210  295 GVKSRSNLAEKVRLSLQYEEAKRsmanlKIElskldsetwpgalDIEKEKLMLINEKEELLKELQFVtprkrtQDELEHL 374
Cdd:COG4026   120 GLKSLQNIPEYNELREELLELKE-----KID-------------EIAKEKEKLTKENEELESELEEL------REEYKKL 175

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 558195210  375 EAERKRLEEELLSVKSTPSQALAERLKLEERRKELVQKLEE 415
Cdd:COG4026   176 REENSILEEEFDNIKSEYSDLKSRFEELLKKRLLEVFSLEE 216

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   164 LKAEISTTRLRVKKLKRELFHMKQELLYKEQGFETLQ-QIDQKMSG-GQSGYELSEAKAILSELK----SIRKAISSGER 237
Cdd:pfam01576  213 LEGESTDLQEQIAELQAQIAELRAQLAKKEEELQAALaRLEEETAQkNNALKKIRELEAQISELQedleSERAARNKAEK 292

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   238 EKQDLMQSLAKLRERFH--LDQTVGISEpdLRSSSvNSQLSLSRQTLDAGSQTDIS--GDIGVKSRSNLAEkvrLSLQYE 313
Cdd:pfam01576  293 QRRDLGEELEALKTELEdtLDTTAAQQE--LRSKR-EQEVTELKKALEEETRSHEAqlQEMRQKHTQALEE---LTEQLE 366

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 558195210   314 EAKRSMANLkielskldsetwpgaldiEKEKLMLINEKEELLKELQFVTPRKRtqdELEHleaERKRLEEELLSVKSTPS 393
Cdd:pfam01576  367 QAKRNKANL------------------EKAKQALESENAELQAELRTLQQAKQ---DSEH---KRKKLEGQLQELQARLS 422

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 558195210   394 QALAERLKLEERRKELVQKLEETTKLTTYLHSQLKSLS 431
Cdd:pfam01576  423 ESERQRAELAEKLSKLQSELESVSSLLNEAEGKNIKLS 460