Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 223 ALYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIAHRLNHTLSE 302
Cdd:COG0666  156 PLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIV 235

                         90       100
                 ....*....|....*....|....*...
gi 748983279 303 RQMVLLHRIAKSGIRDLNDLVMKNALQR 330
Cdd:COG0666  236 KLLLEAGADLNAKDKDGLTALLLAAAAG 263

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 223 ALYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIAHRLNHTLSE 302
Cdd:COG0666  156 PLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIV 235

                         90       100
                 ....*....|....*....|....*...
gi 748983279 303 RQMVLLHRIAKSGIRDLNDLVMKNALQR 330
Cdd:COG0666  236 KLLLEAGADLNAKDKDGLTALLLAAAAG 263

Voltage-dependent potassium channel; Provisional

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 748983279 253 GRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGET 288
Cdd:PLN03192 558 GRTPLHIAASKGYEDCVLVLLKHACNVHIRDANGNT 593

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 204 SEHFEGEkwkhwtsqrafVALYVASHRGHFDAVQYLLEHGA---------SCLSRSP-----LGRTPLHVAAAMGRSDCI 269
Cdd:cd22192   84 SDLYQGE-----------TALHIAVVNQNLNLVRELIARGAdvvspratgTFFRPGPknliyYGEHPLSFAACVGNEEIV 152

                         90       100
                 ....*....|....*....|...
gi 748983279 270 ILLLQHGASIHDRDAKGETPISI 292
Cdd:cd22192  153 RLLIEHGADIRAQDSLGNTVLHI 175

Ubiquitin-like domain; This entry contains ubiquitin-like domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 748983279  115 DMTVRELKEELDLMVGIPFNLQRLQYLDEG-----VLMDDTTL 152
Cdd:pfam14560  22 SLTIEELKEKLELITGTPPSSMRLQLYDDDdnlvaKLDDDDAL 64

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 223 ALYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIAHRLNHTLSE 302
Cdd:COG0666  156 PLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIV 235

                         90       100
                 ....*....|....*....|....*...
gi 748983279 303 RQMVLLHRIAKSGIRDLNDLVMKNALQR 330
Cdd:COG0666  236 KLLLEAGADLNAKDKDGLTALLLAAAAG 263

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 748983279 223 ALYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIAHRLNHT 299
Cdd:COG0666   90 LLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNL 166

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 748983279  223 ALYVASHRGHFDAVQYLLEHGAscLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRD 283
Cdd:pfam12796  33 ALHLAAKNGHLEIVKLLLEHAD--VNLKDNGRTALHYAARSGHLEIVKLLLEKGADINVKD 91

Ankyrin repeats (many copies);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 748983279  223 ALYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLL 273
Cdd:pfam13637   4 ALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLLL 54

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279  96 LRVRLEeTGEMFRVANCRgDMTVRELKEELDLMVGIPFNLQRLQYlDEGVLMDDTTLKFHDVVPGGIISL 165
Cdd:cd17039    1 ITVKTL-DGKTYTVEVDP-DDTVADLKEKIEEKTGIPVEQQRLIY-NGKELKDDKTLSDYGIKDGSTIHL 67

Ankyrin repeats (many copies);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 748983279  239 LLEHG-ASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIA 293
Cdd:pfam13857   1 LLEHGpIDLNRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56

ankyrin repeat protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 224 LYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSdcIILLLQHGASIHDRDAKGETPISiaHRLNHTLSER 303
Cdd:PHA02874 194 LHNAAEYGDYACIKLLIDHGNHIMNKCKNGFTPLHNAIIHNRS--AIELLINNASINDQDIDGSTPLH--HAINPPCDID 269

                         90       100
                 ....*....|....*....|....*...
gi 748983279 304 QM-VLLHRIAKSGIRDLN-----DLVMK 325
Cdd:PHA02874 270 IIdILLYHKADISIKDNKgenpiDTAFK 297

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO(3) anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. The ANK repeats are found to form a contiguous spiral stack such that ion transporters like the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 748983279  253 GRTPLHVAAAM-GRSDCIILLLQHGASIHDRD 283
Cdd:pfam00023   2 GNTPLHLAAGRrGNLEIVKLLLSKGADVNARD 33

ubiquitin-like (Ubl) domain found in IQ and ubiquitin-like domain-containing protein (IQUB) and similar proteins; IQUB is an IQ motif and ubiquitin domain-containing protein that may play roles in cilia formation and/or maintenance. It contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 748983279 104 GEMFRVAnCRGDMTVRELKEELDLMVGIPFNLQRLQYLDEgVLMDDTTLKFHDVVPGGIISL 165
Cdd:cd17061   13 GQVITLA-FTLGQTIGELKEHFSSELKIPPDVLQIMFDGK-LVEDNTTLVDLGVRPNGTIQL 72

Ankyrin repeats (many copies);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 748983279  253 GRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIA 293
Cdd:pfam13637   1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFA 41

ankyrin repeat protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 224 LYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIA 293
Cdd:PHA02874 161 IHIAIKHNFFDIIKLLLEKGAYANVKDNNGESPLHNAAEYGDYACIKLLIDHGNHIMNKCKNGFTPLHNA 230

Ankyrin repeats (3 copies);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 748983279  257 LHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIAHRLNHT 299
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHL 43

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 748983279 115 DMTVRELKEELDLMVGIPFNLQRLQYldEG-VLMDDTTLKFHDV 157
Cdd:cd01809   20 EITVKEFKEHIASSVNIPAEKQRLIF--QGrVLQDDKKLKEYDV 61

Ankyrin repeats (many copies);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 748983279  214 HWTSQRAFVALYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVA 260
Cdd:pfam13857  10 NRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 224 LYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKG-------------ETPI 290
Cdd:PTZ00322 119 LHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRHSQCHFELGANAkpdsftgkppsleDSPI 198

                 ....
gi 748983279 291 SIAH 294
Cdd:PTZ00322 199 SSHH 202

ankyrin repeat protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 748983279 233 FDAVQYLLEHGASCLSRSP-LGRTPLHVAaaMGRSDCIILLLQHGASIHDRDAKGETPISIA 293
Cdd:PHA02878 248 YDILKLLLEHGVDVNAKSYiLGLTALHSS--IKSERKLKLLLEYGADINSLNSYKLTPLSSA 307

ankyrin-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 748983279 236 VQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPISIAHRLNHT 299
Cdd:PHA03095 240 VLPLLIAGISINARNRYGQTPLHYAAVFNNPRACRRLIALGADINAVSSDGNTPLSLMVRNNNG 303

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 748983279 115 DMTVRELKEELDLMVGIPFNLQRLQYldEG-VLMDDTTLKFHDVVPGGIISL 165
Cdd:cd16106   20 DATVLELKELIAEKSDIPAEQQRLIY--KGkILKDEETLSSYKIQDGHTVHL 69

ankyrin repeat protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 748983279 224 LYVASHRGHFDAVQYLLEHGASCLSRSPLGRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGETPI 290
Cdd:PHA02874 128 LHYAIKKGDLESIKMLFEYGADVNIEDDNGCYPIHIAIKHNFFDIIKLLLEKGAYANVKDNNGESPL 194

transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ Channel (TRP-CC) Family (TC. 1.A.4)The TRP-CC family has also been called the store-operated calcium channel (SOC) family. The prototypical members include the Drosophila retinal proteinsTRP and TRPL (Montell and Rubin, 1989; Hardie and Minke, 1993). SOC members of the family mediate the entry of extracellular Ca2+ into cells in responseto depletion of intracellular Ca2+ stores (Clapham, 1996) and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CCfamily, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor (TC #1.A.3.2.1). This interaction is apparently required for IP3 tostimulate Ca2+ release via Htrp3. The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin (the ?hot? ingredient in chili peppers) and servesas a heat-activated ion channel in the pain pathway (Caterina et al., 1997), is also a member of this family. The stretch-inhibitable non-selective cation channel(SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SICtransport monovalent cations as well as Ca2+. VR1 is about 10x more permeable to Ca2+ than to monovalent ions. Ca2+ overload probably causes cell deathafter chronic exposure to capsaicin. (McCleskey and Gold, 1999). [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279  223 ALYVASHRGHFDAVQYLLEHGAS---------CLSRSPL-----GRTPLHVAAAMGRSDCIILLLQHGASIHDRDAKGET 288
Cdd:TIGR00870 131 ALHLAAHRQNYEIVKLLLERGASvparacgdfFVKSQGVdsfyhGESPLNAAACLGSPSIVALLSEDPADILTADSLGNT 210

Transient Receptor Potential channel, Vanilloid subfamily (TRPV); The vanilloid TRP subfamily (TRPV), named after the vanilloid receptor 1 (TRPV1), consists of six members: four thermo-sensing channels (TRPV1, TRPV2, TRPV3, and TRPV4) and two Ca2+ selective channels (TRPV5 and TRPV6). The calcium-selective channels TRPV5 and TRPV6 can be heterotetramers and are important for general Ca2+ homeostasis. All four channels within the TRPV1-4 group show temperature-invoked currents when expressed in heterologous cell systems, ranging from activation at ~25C for TRPV4 to ~52C for TRPV2. The structure of TRPV shows the typical topology features of all Transient Receptor Potential (TRP) ion channel family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6 and large intracellular N- and C-terminal domains. The TRP family consists of membrane proteins that function as ion channels that communicate between the cell and its environment, by a vast array of physical or chemical stimuli, including radiation (in the form of temperature, infrared ,or light) and pressure (osmotic or mechanical). TRP channels are formed by a tetrameric complex of channel subunits. Based on sequence identity, the mammalian TRP channel family is classified into six subfamilies, with significant sequence similarity within the transmembrane domains, but very low similarity in their N- and C-terminal cytoplasmic regions. The six subfamilies are named based on their first member: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystic).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 748983279 170 HDGWTELVLAAVEGDPSKLSCLGLTEDSfyrtANSEHFEGEkwkhwtsqrafVALYVASHRGHFDAVQYLLEHGASC--- 246
Cdd:cd21882   38 NDGVNEAIMLLLEAAPDSGNPKELVNAP----CTDEFYQGQ-----------TALHIAIENRNLNLVRLLVENGADVsar 102

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 748983279 247 -----LSRSP-----LGRTPLHVAAAMGRSDCIILLLQHGASIHD---RDAKGETPISI 292
Cdd:cd21882  103 atgrfFRKSPgnlfyFGELPLSLAACTNQEEIVRLLLENGAQPAAleaQDSLGNTVLHA 161

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 748983279 117 TVRELKEELDLMVGIPFNLQRLQYLDEGVLMDDTTLKFHDVVPGGIISL 165
Cdd:cd01800   33 TISVLKEKIHEELGMPANKQKLQVEGGGFLKDSNSLAFYNLGSGTVLTL 81