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Conserved domains on  [gi|578822486|ref|XP_006719011|]
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phospholipid transfer protein C2CD2L isoform X2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
SMP_SF super family cl45903
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP ...
84-223 4.14e-84

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP domain is a lipid transport domain found in phospholipid transfer proteins such as synaptotagmin family proteins, tricalbin (TCB) family proteins, maintenance of mitochondrial morphology protein 1 (MMM1), mitochondrial distribution and morphology protein 12 (MDM12), mitochondrial distribution and morphology protein 34 (MDM34), PDZ domain-containing protein 8 (PDZD8), testis-expressed protein 2 (TEX2), meiotically up-regulated gene 190 protein (Mug190), C2 domain-containing protein 2 (C2CD2) and C2 domain-containing protein 2-like (C2CD2L). The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP (tubular lipid-binding proteins). It adopts a TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.


The actual alignment was detected with superfamily member cd21683:

Pssm-ID: 459248  Cd Length: 177  Bit Score: 262.33  E-value: 4.14e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486  84 GVRGLLASLFAFKSFRENWQRAWVRALNEQACRNGSSIQIAFEEVPQLPPRASISHVTCVDQSEHTMVLRCQLSAEEVRF 163
Cdd:cd21683    1 GAKGLLTSLFAFKSFRENWQRAWVRALNEQACRNGSSLQITFEESPQLPASASISHVTCTDQSDHSMVLHCNLSADAVKF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486 164 PVSVTQQSPAAVSMETYHVTLTLPPTQ-------------------------------------RGEEQVELSTIEELIK 206
Cdd:cd21683   81 PVSVTQQSPAAVSMDTYQVTLAPLQAQvevcleevenegllvswtfkdrpdlsltvtprqqqqeGNEGKADLSTIQDLIE 160
                        170
                 ....*....|....*..
gi 578822486 207 DAIVSTQPAMMVNLRAC 223
Cdd:cd21683  161 DTLVSTQPAMILNLKAC 177
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
263-375 8.42e-13

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.


The actual alignment was detected with superfamily member cd08678:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 126  Bit Score: 65.47  E-value: 8.42e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486 263 NELEGTEELCCVAELDNPMQQKWTKPARAGSEVEWTEDLALDLGPQSRELTLKVLRSSSCGDTELLGQATLPVGSPSRPL 342
Cdd:cd08678   12 SEAAGSSNPYCVLEMDEPPQKYQSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNGKKSDSKFLGLAIVPFDELRKNP 91
                         90       100       110
                 ....*....|....*....|....*....|...
gi 578822486 343 SRRQLCPLTPGPGKALGPAATMAVELHYEEGSP 375
Cdd:cd08678   92 SGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAE 124
 
Name Accession Description Interval E-value
SMP_C2CD2L cd21683
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 ...
84-223 4.14e-84

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 domain-containing protein 2-like (C2CD2L); C2CD2L, also called phospholipid transfer protein C2CD2L, or C2CD2-like, or transmembrane protein 24 (TMEM24), is a lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane. It is a Ca2+-regulated component of endoplasmic reticulum (ER)-plasma membrane contacts in mammalian neurons. This model corresponds to the SMP domain of C2CD2L, which may be implicated in lipid transport.


Pssm-ID: 439239  Cd Length: 177  Bit Score: 262.33  E-value: 4.14e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486  84 GVRGLLASLFAFKSFRENWQRAWVRALNEQACRNGSSIQIAFEEVPQLPPRASISHVTCVDQSEHTMVLRCQLSAEEVRF 163
Cdd:cd21683    1 GAKGLLTSLFAFKSFRENWQRAWVRALNEQACRNGSSLQITFEESPQLPASASISHVTCTDQSDHSMVLHCNLSADAVKF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486 164 PVSVTQQSPAAVSMETYHVTLTLPPTQ-------------------------------------RGEEQVELSTIEELIK 206
Cdd:cd21683   81 PVSVTQQSPAAVSMDTYQVTLAPLQAQvevcleevenegllvswtfkdrpdlsltvtprqqqqeGNEGKADLSTIQDLIE 160
                        170
                 ....*....|....*..
gi 578822486 207 DAIVSTQPAMMVNLRAC 223
Cdd:cd21683  161 DTLVSTQPAMILNLKAC 177
SMP_C2CD2L pfam18696
Synaptotagmin-like, mitochondrial and lipid-binding domain; This is a lipid transport domain ...
102-216 4.25e-45

Synaptotagmin-like, mitochondrial and lipid-binding domain; This is a lipid transport domain found in phospholipid transfer proteins such as C2CD2L-like (also known as TMEM24). The TMEM24-SMP domain is shown to bind glycerolipids with a preference for phosphatidylinositol (PI).The bound PI is then transferred to the plasma membrane (PM) where it is converted to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to replenish pools of this lipid hydrolyzed during glucose-stimulated signaling. PI(4,5)P2 is required for Ca2+-dependent exocytosis hence, the SMP domain of TMEM24 is essential for sustaining the intracellular Ca2+ oscillations that trigger bursts of insulin granule release and hence insulin secretion. The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP for (tubular lipid-binding proteins) it adopts TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.


Pssm-ID: 465835  Cd Length: 152  Bit Score: 157.81  E-value: 4.25e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486  102 WQRAWVRALNEQACRNGSSIQIAFEEVP-QLPPRASISHVTCVDQSEHTMVLRCQLSAEEVRFPVSVTQQSPAAVSMETY 180
Cdd:pfam18696   1 WQRAWVRALNEEACRRGGPLQLTFEEDGlQQPLELAVSQVSSFDKSAQEKVVSCHVVGEALQFPVSVTQQSPAAVSPQTY 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578822486  181 HVTLTLPPTQ------------------------------------RGEEQVELSTIEELIKDAIVSTQPAM 216
Cdd:pfam18696  81 QVTLSPLHLQlelhmeekeediqiswsfshlpelslqvtpkaqqeqVNETAAVSETLKDLLKDLLSSASPSV 152
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
263-375 8.42e-13

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. 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.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 65.47  E-value: 8.42e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486 263 NELEGTEELCCVAELDNPMQQKWTKPARAGSEVEWTEDLALDLGPQSRELTLKVLRSSSCGDTELLGQATLPVGSPSRPL 342
Cdd:cd08678   12 SEAAGSSNPYCVLEMDEPPQKYQSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNGKKSDSKFLGLAIVPFDELRKNP 91
                         90       100       110
                 ....*....|....*....|....*....|...
gi 578822486 343 SRRQLCPLTPGPGKALGPAATMAVELHYEEGSP 375
Cdd:cd08678   92 SGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAE 124
 
Name Accession Description Interval E-value
SMP_C2CD2L cd21683
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 ...
84-223 4.14e-84

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 domain-containing protein 2-like (C2CD2L); C2CD2L, also called phospholipid transfer protein C2CD2L, or C2CD2-like, or transmembrane protein 24 (TMEM24), is a lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane. It is a Ca2+-regulated component of endoplasmic reticulum (ER)-plasma membrane contacts in mammalian neurons. This model corresponds to the SMP domain of C2CD2L, which may be implicated in lipid transport.


Pssm-ID: 439239  Cd Length: 177  Bit Score: 262.33  E-value: 4.14e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486  84 GVRGLLASLFAFKSFRENWQRAWVRALNEQACRNGSSIQIAFEEVPQLPPRASISHVTCVDQSEHTMVLRCQLSAEEVRF 163
Cdd:cd21683    1 GAKGLLTSLFAFKSFRENWQRAWVRALNEQACRNGSSLQITFEESPQLPASASISHVTCTDQSDHSMVLHCNLSADAVKF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486 164 PVSVTQQSPAAVSMETYHVTLTLPPTQ-------------------------------------RGEEQVELSTIEELIK 206
Cdd:cd21683   81 PVSVTQQSPAAVSMDTYQVTLAPLQAQvevcleevenegllvswtfkdrpdlsltvtprqqqqeGNEGKADLSTIQDLIE 160
                        170
                 ....*....|....*..
gi 578822486 207 DAIVSTQPAMMVNLRAC 223
Cdd:cd21683  161 DTLVSTQPAMILNLKAC 177
SMP_C2CD2-like cd21664
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 ...
85-223 1.86e-45

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 domain-containing protein 2-like (C2CD2L) and similar proteins; This family includes C2 domain-containing protein 2 (C2CD2) and C2CD2-like (C2CD2L). C2CD2 (also called transmembrane protein 24-like or TMEM24L), may be a lipid-binding protein that shows high sequence similarity with C2 domain-containing protein 2-like (C2CD2L; also called transmembrane protein 24 or TMEM24). C2CD2L is a lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum (ER) to the cell membrane. It is a Ca2+-regulated component of ER-plasma membrane contacts in mammalian neurons. This model corresponds to the SMP domain of C2CD2 and C2CD2L which binds glycerolipids with a preference for phosphatidylinositol (PI). The bound PI is then transferred to the plasma membrane (PM) where it is converted to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to replenish pools of this lipid hydrolyzed during glucose-stimulated signaling. PI(4,5)P2 is required for Ca2+-dependent exocytosis; hence, the SMP domain of TMEM24 is essential for sustaining the intracellular Ca2+ oscillations that trigger bursts of insulin granule release and subsequent insulin secretion.


Pssm-ID: 439224  Cd Length: 175  Bit Score: 159.44  E-value: 1.86e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486  85 VRGLLASLFAFK-SFRENWQRAWVRALNEQACRNGSSIQIAFEEVPQLPPRASISHVTCVDQSEHTMVLRCQLSAEEVRF 163
Cdd:cd21664    1 WLNSVLNWIYTQyCNTPELVEAWLKALNEQARRAGSSVQVTFERIQSGSLPPKFTHVSTVAEPNDSLVVTCQVESEGLRF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486 164 PVSVTQQSPAAVSMETYHVTLTLPPTQ-----------------------------------RGEEQVELSTIEELIKDA 208
Cdd:cd21664   81 QVFATQQTAQSVKLSNCDVSVTKLSGKlrchgrtlgeelqisvsfedrpdlklnikpkngspTAEDSVDLDVVEEIVRNA 160
                        170
                 ....*....|....*
gi 578822486 209 IVSTQPAMMVNLRAC 223
Cdd:cd21664  161 IASATTTFVLPTQAT 175
SMP_C2CD2L pfam18696
Synaptotagmin-like, mitochondrial and lipid-binding domain; This is a lipid transport domain ...
102-216 4.25e-45

Synaptotagmin-like, mitochondrial and lipid-binding domain; This is a lipid transport domain found in phospholipid transfer proteins such as C2CD2L-like (also known as TMEM24). The TMEM24-SMP domain is shown to bind glycerolipids with a preference for phosphatidylinositol (PI).The bound PI is then transferred to the plasma membrane (PM) where it is converted to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to replenish pools of this lipid hydrolyzed during glucose-stimulated signaling. PI(4,5)P2 is required for Ca2+-dependent exocytosis hence, the SMP domain of TMEM24 is essential for sustaining the intracellular Ca2+ oscillations that trigger bursts of insulin granule release and hence insulin secretion. The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP for (tubular lipid-binding proteins) it adopts TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.


Pssm-ID: 465835  Cd Length: 152  Bit Score: 157.81  E-value: 4.25e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486  102 WQRAWVRALNEQACRNGSSIQIAFEEVP-QLPPRASISHVTCVDQSEHTMVLRCQLSAEEVRFPVSVTQQSPAAVSMETY 180
Cdd:pfam18696   1 WQRAWVRALNEEACRRGGPLQLTFEEDGlQQPLELAVSQVSSFDKSAQEKVVSCHVVGEALQFPVSVTQQSPAAVSPQTY 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578822486  181 HVTLTLPPTQ------------------------------------RGEEQVELSTIEELIKDAIVSTQPAM 216
Cdd:pfam18696  81 QVTLSPLHLQlelhmeekeediqiswsfshlpelslqvtpkaqqeqVNETAAVSETLKDLLKDLLSSASPSV 152
SMP_C2CD2 cd21682
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 ...
87-185 3.20e-19

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 domain-containing protein 2 (C2CD2); C2CD2, also called transmembrane protein 24-like (TMEM24L), may be a lipid-binding protein that shows high sequence similarity with C2 domain-containing protein 2-like (C2CD2L; also transmembrane protein 24 or TMEM24). C2CD2L is a lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane. It is a Ca2+-regulated component of endoplasmic reticulum (ER)-plasma membrane contacts in mammalian neurons. This model corresponds to the SMP domain of C2CD2, which may be implicated in lipid transport.


Pssm-ID: 439238  Cd Length: 175  Bit Score: 85.38  E-value: 3.20e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486  87 GLLASLFAFKSFRENWQRAWVRALNEQACRNGSSIQIAFEEVPQLPPRASISHVTCVDQSEHTMVLRCQLSAEEVRFPVS 166
Cdd:cd21682    4 ALLSWALSLKSWRSQWRRAWVTALNEEARKRGGPLLLTFEEDGLQQLELVVSQVSSFVKSAQEKVVSCQVVGEKLQFSVS 83
                         90
                 ....*....|....*....
gi 578822486 167 VTQQSPAAVSMETYHVTLT 185
Cdd:cd21682   84 AAPASPTAAGPQLYSVKLS 102
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
263-375 8.42e-13

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. 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.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 65.47  E-value: 8.42e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822486 263 NELEGTEELCCVAELDNPMQQKWTKPARAGSEVEWTEDLALDLGPQSRELTLKVLRSSSCGDTELLGQATLPVGSPSRPL 342
Cdd:cd08678   12 SEAAGSSNPYCVLEMDEPPQKYQSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNGKKSDSKFLGLAIVPFDELRKNP 91
                         90       100       110
                 ....*....|....*....|....*....|...
gi 578822486 343 SRRQLCPLTPGPGKALGPAATMAVELHYEEGSP 375
Cdd:cd08678   92 SGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAE 124
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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