Diacylglycerol kinase accessory domain (presumed); Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. DAG can be produced from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phosphoinositide-specific phospholipase C and by the degradation of phosphatidylcholine (PC) by a phospholipase C or the concerted actions of phospholipase D and phosphatidate phosphohydrolase. This domain might either be an accessory domain or else contribute to the catalytic domain. Bacterial homologues are known.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   723 VMNNYFGIGLDAKISLDFNNKRDEHPEKCRSRTKNMMWYGVLGTKELLHRTYKNLEQKVLLECDGRPIPLP-SLQGIAVL 801
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   802 NIPSYAGGTNFWGGT-KEDDTFAAPSFDDKILEVVAVFGSMQMAVSRVIRLQHHRIAQCRTVKISILGDEGVPVQVDGEA 880
Cdd:smart00045   81 NIPSYGGGTNLWGTTdKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSKTIPMQVDGEP 160

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta (DAG kinase delta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase delta, also called 130 kDa diacylglycerol kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. DAG kinase delta contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250  100 ALKTVQNREHFEPTQYSMDHFSGMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCKWTTLA 179
Cdd:cd20847      1 ALKSVQNREHFESTQYSMDHFSGMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCKWTTLA 80

                   ....*
gi 1034617250  180 SIGKD 184
Cdd:cd20847     81 SIGKD 85

SAM domain of diacylglycerol kinase delta; SAM (sterile alpha motif) domain of DGK-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK-delta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. In particular DGK-delta is involved in the regulation of clathrin-dependent endocytosis. The SAM domain of DGK-delta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-eta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it inhibits the translocation of the protein to the plasma membrane from the cytoplasm. The SAM domain also can bind Zn at multiple (not conserved) sites driving the formation of highly ordered large sheets of polymers, thus suggesting that Zn may play important role in the function of DCK-delta.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034617250 1101 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:cd09575      1 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDVRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 65

Diacylglycerol kinase accessory domain (presumed); Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. DAG can be produced from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phosphoinositide-specific phospholipase C and by the degradation of phosphatidylcholine (PC) by a phospholipase C or the concerted actions of phospholipase D and phosphatidate phosphohydrolase. This domain might either be an accessory domain or else contribute to the catalytic domain. Bacterial homologues are known.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   723 VMNNYFGIGLDAKISLDFNNKRDEHPEKCRSRTKNMMWYGVLGTKELLHRTYKNLEQKVLLECDGRPIPLP-SLQGIAVL 801
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   802 NIPSYAGGTNFWGGT-KEDDTFAAPSFDDKILEVVAVFGSMQMAVSRVIRLQHHRIAQCRTVKISILGDEGVPVQVDGEA 880
Cdd:smart00045   81 NIPSYGGGTNLWGTTdKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSKTIPMQVDGEP 160

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   15 IKEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSIIFDEVDLTDASVAESSTKNVNNSFTVITPCRKLILCADNRKEM 94
Cdd:cd13274      1 IKEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKDSKSLIFEEIDLSDASVAECSTKNVNNSFTVITPFRKLILCAESRKEM 80

                           90
                   ....*....|....*..
gi 1034617250   95 EDWIAALKTVQNREHFE 111
Cdd:cd13274     81 EEWISALKTVQQREFYE 97

Diacylglycerol kinase catalytic domain (presumed); Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. DAG can be produced from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phosphoinositide-specific phospholipase C and by the degradation of phosphatidylcholine (PC) by a phospholipase C or the concerted actions of phospholipase D and phosphatidate phosphohydrolase. This domain is presumed to be the catalytic domain. Bacterial homologues areknown.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   283 LVFVNSKSGDNQGVKFLRRFKQLLNPAQVFDLMNGGPHLGLRLFQKFDTF-RILVCGGDGSVGWVLSEIDSLNLHKQC-Q 360
Cdd:smart00046    1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPLPEpP 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 1034617250   361 LGVLPLGTGNDLARVLGWGSACDDDTQLPqILEKLERASTKMLDR 405
Cdd:smart00046   81 VAVLPLGTGNDLARSLGWGGGYDGEKLLK-TLRDALESDTVKLDR 124

second protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta (DAG kinase delta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase delta, also called 130 kDa diacylglycerol kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. DAG kinase delta contains two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034617250  191 GIAMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLLTKCPLGLC 251
Cdd:cd20893      1 GISMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKELLLTKCPLGQC 61

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034617250  1102 VHLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERR-DLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEeDLKELGITKLGHRKKILKAIQKL 65

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 1034617250   124 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 173
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

Phosphatidylglycerol kinase, diacylglycerol kinase family [Lipid transport and metabolism, General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250  282 LLVFVNSKSGDNQGVKFLRRFKQLLN----PAQVFDLMNGGPhlGLRLFQK-----FDtfRILVCGGDGSVGWVLSEIds 352
Cdd:COG1597      5 ALLIVNPASGRGRAARLLERLVAALRaaglEVEVLETESPGD--ATELAREaaaegAD--LVVAAGGDGTVNEVANGL-- 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1034617250  353 lnLHKQCQLGVLPLGTGNDLARVLGWgsacddDTQLPQILEKLERASTKMLD 404
Cdd:COG1597     79 --AGTGPPLGILPLGTGNDFARALGI------PLDPEAALEALLTGRTRRID 122

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1034617250  124 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 173
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPEC 50

Phosphatidylglycerol kinase, diacylglycerol kinase family [Lipid transport and metabolism, General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250  726 NYFGIGLDAKISLDFNNKRdehpekcrSRTKNMMWYGVLGTKELlhRTYKNLEqkVLLECDGRPIPLPSLQgIAVLNIPS 805
Cdd:COG1597    133 NVAGIGFDAEVVERANRAL--------KRRLGKLAYVLAALRAL--LRYRPFR--LRIELDGEEIEGEALL-VAVGNGPY 199

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250  806 YAGGTNFwggtkeddtFAAPSFDDKILEVVAV----FGSMQMAVSRVIR---LQHHRIAQCRTVKISILGDEGVPVQVDG 878
Cdd:COG1597    200 YGGGLRL---------APDASLDDGLLDVVVVrplsRLRLLRLLPRLLRgrhLRHPGVRYFRAREVEIESDRPLPVQLDG 270

                          170
                   ....*....|....*.
gi 1034617250  879 EA-WVQPPGYIRIVHK 893
Cdd:COG1597    271 EPlGLATPLEFEVLPG 286

hypothetical protein; Provisional

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034617250  334 ILVCGGDGSVGWVLSEIdslnLHKQCQLGVLPLGTGNDLARVL-GWGSACDDdtqLPQILEKLERASTKMLD 404
Cdd:PRK12361   301 VIACGGDGTVTEVASEL----VNTDITLGIIPLGTANALSHALfGLGSKLIP---VEQACDNIIQGHTQRID 365

Diacylglycerol kinase accessory domain (presumed); Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. DAG can be produced from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phosphoinositide-specific phospholipase C and by the degradation of phosphatidylcholine (PC) by a phospholipase C or the concerted actions of phospholipase D and phosphatidate phosphohydrolase. This domain might either be an accessory domain or else contribute to the catalytic domain. Bacterial homologues are known.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   723 VMNNYFGIGLDAKISLDFNNKRDEHPEKCRSRTKNMMWYGVLGTKELLHRTYKNLEQKVLLECDGRPIPLP-SLQGIAVL 801
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   802 NIPSYAGGTNFWGGT-KEDDTFAAPSFDDKILEVVAVFGSMQMAVSRVIRLQHHRIAQCRTVKISILGDEGVPVQVDGEA 880
Cdd:smart00045   81 NIPSYGGGTNLWGTTdKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSKTIPMQVDGEP 160

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   15 IKEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSIIFDEVDLTDASVAESSTKNVNNSFTVITPCRKLILCADNRKEM 94
Cdd:cd13274      1 IKEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKDSKSLIFEEIDLSDASVAECSTKNVNNSFTVITPFRKLILCAESRKEM 80

                           90
                   ....*....|....*..
gi 1034617250   95 EDWIAALKTVQNREHFE 111
Cdd:cd13274     81 EEWISALKTVQQREFYE 97

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase eta (DAG kinase eta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. The diacylglycerol kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase eta contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   95 EDWIAALKTVQNREHFEPTQYSMDHFSGMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCK 174
Cdd:cd20848      1 EDWISSLKSVQSREHYETAQFNVEHFSGMHNWYACSHARPTFCNVCRESLSGVTSHGLSCEVCKFKAHKRCAVRATNNCK 80

                   ....*.
gi 1034617250  175 WTTLAS 180
Cdd:cd20848     81 WTTLAS 86

SAM domain of diacylglycerol kinase delta; SAM (sterile alpha motif) domain of DGK-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK-delta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. In particular DGK-delta is involved in the regulation of clathrin-dependent endocytosis. The SAM domain of DGK-delta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-eta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it inhibits the translocation of the protein to the plasma membrane from the cytoplasm. The SAM domain also can bind Zn at multiple (not conserved) sites driving the formation of highly ordered large sheets of polymers, thus suggesting that Zn may play important role in the function of DCK-delta.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034617250 1101 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:cd09575      1 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDVRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 65

SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain of DGK-eta-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DGK proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers between the SAM domains of DGK delta and eta proteins. The oligomerization plays a role in the regulation of DGK intracellular localization.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034617250 1101 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:cd09507      1 PVTNWTTEEVGAWLESLQLGEYRDIFARNDIRGSELLHLERRDLKDLGITKVGHVKRILQAIKDL 65

second protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase eta (DAG kinase eta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. The diacylglycerol kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase eta contains two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034617250  191 GIAMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLLTKCPLGLCK 252
Cdd:cd20894      1 GIAMPHQWLEGNLPVSAKCSVCDKTCGSVLRLQDWRCLWCKAMVHTACKDQYPRKCPLGQCR 62

SAM domain of diacylglycerol kinase eta; SAM (sterile alpha motif) domain of DGK-eta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases. The SAM domain is located at the C-terminus of two out of three isoforms of DGK-eta protein. DGK-eta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DCK-eta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-delta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it is responsible for sustained endosomal localization of the protein and resulted in negative regulation of DCK-eta catalytic activity.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034617250 1101 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:cd09576      1 PVQKWGTDEVAAWLDLLSLGEYKEIFIRHDIRGSELLHLERRDLKDLGIPKVGHMKRILQGIKEL 65

second protein kinase C conserved region 1 (C1 domain) found in the diacylglycerol kinase family; The diacylglycerol kinase (DGK, EC 2.7.1.107) family of enzymes plays critical roles in lipid signaling pathways by converting diacylglycerol to phosphatidic acid, thereby downregulating signaling by the former and upregulating signaling by the latter second messenger. Ten DGK family isozymes have been identified to date, which possess different interaction motifs imparting distinct temporal and spatial control of DGK activity to each isozyme. They have been classified into five types (I-V), according to domain architecture and some common features. All DGK isozymes, except for DGKtheta, contain two copies of the C1 domain. This model corresponds to the second one. DGKtheta harbors three C1 domains. Its third C1 domain is included here. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1034617250  196 HQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLL-TKCPLG 249
Cdd:cd20805      1 HHWVEGNLPSGAKCSVCGKKCGSSFGLAGYRCSWCKRTVHSECIDKLGpEECDLG 55

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034617250  1102 VHLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERR-DLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEeDLKELGITKLGHRKKILKAIQKL 65

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034617250 1101 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKELS 1166
Cdd:cd09506      1 PVHEWTVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKLL 66

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034617250 1109 EVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKE 1164
Cdd:cd09487      1 DVAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQR 56

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034617250 1103 HLWGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:pfam00536    1 DGWSVEDVGEWLESIGLGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   16 KEGMLTKQNNSFQRS-KRRYFKLRGRTLYYAKTAKSIIF---DEVDLTD-ASVAESSTKNVNNSFTVITP-CRKLILCAD 89
Cdd:cd00821      1 KEGYLLKRGGGGLKSwKKRWFVLFEGVLLYYKSKKDSSYkpkGSIPLSGiLEVEEVSPKERPHCFELVTPdGRTYYLQAD 80

                           90
                   ....*....|..
gi 1034617250   90 NRKEMEDWIAAL 101
Cdd:cd00821     81 SEEERQEWLKAL 92

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   16 KEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSII-FDEVDLTDAS-VAESSTKNVNNSFTVITPCRKLILCADNRKE 93
Cdd:cd10573      5 KEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDTKpIRVLDLRECSsVQRDYSQGKVNCFCLVFPERTFYMYANTEEE 84

                   ....*....
gi 1034617250   94 MEDWIAALK 102
Cdd:cd10573     85 ADEWVKLLK 93

first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type I DAG kinases (DGKs) contain EF-hand structures that bind Ca(2+) and recoverin homology domains, in addition to C1 and catalytic domains that are present in all DGKs. Type I DGKs, regulated by calcium binding, include three DGK isozymes (alpha, beta and gamma). DAG kinase alpha, also called 80 kDa DAG kinase, or diglyceride kinase alpha (DGK-alpha), is active upon cell stimulation, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. DAG kinase beta, also called 90 kDa DAG kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. DGK-alpha contains atypical C1 domains, while DGK-beta and DGK-gamma contain typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1034617250  122 GMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 173
Cdd:cd20799      4 GQHVWRLKHFNKPAYCNVCENMLVGLRKQGLCCTFCKYTVHERCVSRAPASC 55

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   14 IIKEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSI-IFDEVDLTD-ASVAESSTKNVNNSFTVITPCRKLILCADNR 91
Cdd:cd13255      6 VLKAGYLEKKGERRKTWKKRWFVLRPTKLAYYKNDKEYrLLRLIDLTDiHTCTEVQLKKHDNTFGIVTPARTFYVQADSK 85

                           90
                   ....*....|
gi 1034617250   92 KEMEDWIAAL 101
Cdd:cd13255     86 AEMESWISAI 95

SAM domain of WDSUB1 proteins; SAM (sterile alpha motif) domain of WDSUB1 subfamily proteins is a putative protein-protein interaction domain. Proteins of this group contain multiple domains: SAM, one or more WD40 repeats and U-box (derived version of the RING-finger domain). Apparently the WDSUB1 subfamily proteins participate in protein degradation through ubiquitination, since U-box domain are known as a member of E3 ubiquitin ligase family, while SAM and WD40 domains most probably are responsible for an E2 ubiquitin-conjugating enzyme binding and a target protein binding.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034617250 1105 WGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDL-KDLGVTKVGHMKRILCGIKEL 1165
Cdd:cd09505      5 WSEEDVCTWLRSIGLEQYVEVFRANNIDGKELLNLTKESLsKDLKIESLGHRNKILRKIEEL 66

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1034617250  124 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 173
Cdd:cd20842     35 HTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCKFNCHKRCAPKVPNNC 84

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1034617250  124 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 173
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPEC 50

protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein BZZ1 and similar proteins; BZZ1 is a syndapin-like F-BAR protein that plays a role in endocytosis and trafficking to the vacuole. It functions with type I myosins to restore polarity of the actin cytoskeleton after NaCl stress. BZZ1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. Schizosaccharomyces pombe BZZ1 also harbors a C1 domain, but Saccharomyces cerevisiae BZZ1 doesn't have any. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034617250  123 MHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 173
Cdd:cd20824      1 PHNFKPHSFSIPTKCDYCGEKIWGLSKKGLSCKDCGFNCHIKCELKVPPEC 51

SAM domain of Samd14 subfamily; SAM (sterile alpha motif) domain of SamD14 (or FAM15A) subfamily is a putative protein-protein interaction domain. SAM is widespread domain in proteins involved in signal transduction and regulation. In many cases SAM mediates homodimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034617250 1105 WGTEEVAAWLEHLSLCEYKDIFTRHDIRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 1165
Cdd:cd09530      3 WDTEDVAEWIEGLGFPQYRECFTTNFIDGRKLILVDASTLPRMGVTDFEHIKAIARKIREL 63

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG kinase beta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase beta, also called 90 kDa diacylglycerol kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DAG kinase beta contains two copies of the C1 domain. This model corresponds to the first one. DGK-beta contains typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034617250  122 GMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCKWTTLAS 180
Cdd:cd20845      6 GQHVWRLKHFNKPAYCNLCLNMLVGLGKQGLCCSFCKYTVHERCVQRAPASCIKTYVKS 64

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034617250   13 TIIKEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSIIF--DEVDLTDASVAESSTKNVNN--SFTVITPCRKLILCA 88
Cdd:cd13215     20 AVIKSGYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTDLYFpaGTIDLRYATSIELSKSNGEAttSFKIVTNSRTYKFKA 99

                           90
                   ....*....|....*..
gi 1034617250   89 DNRKEMEDWIAALKTVQ 105
Cdd:cd13215    100 DSETSADEWVKALKKQI 116