NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|427918117|ref|NP_001258779|]
View 

phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 isoform C2 [Homo sapiens]

Protein Classification

PTEN domain-containing protein( domain architecture ID 13212235)

phosphatase and tensin homolog (PTEN) protein tyrosine phosphatase (PTP) and C2 domain-containing protein; similar to human TPIP splice-variant TPIP-C2

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
 62-192 2.68e-45

C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key form, of the PTEN protein, phosphatidyl-inositol triphosphate phosphatase, and it is the C-terminus. This domain may well include a CBR3 loop which means it plays a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc (pfam00782) suggesting that the C2 domain productively positions the catalytic part of the protein onto the membrane.


:

Pssm-ID: 463081  Cd Length: 133  Bit Score: 146.27  E-value: 2.68e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 427918117   62 PPRRILFIKRFIIYSI----RGDVCDLKVQVVMEKKVVFSStsLGNCSILHDIETDKILINVYDGPPLYDDVKVQFFSSN 137
Cdd:pfam10409   1 PPPKPLTLHSIILHGIpnfkSGGGCRPYIRIYQNKKKVFST--SGKYKKLKEYQQDDCVILFPKGIPVQGDVLVEFYHKG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 427918117  138 LPKYYDNCPFFFWFNTSFIQNNRLCLPRNELDNPHKQKAWKIYPPEFAVEILFGE 192
Cdd:pfam10409  79 SDLLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDKKDKRFPKDFKVELLFSE 133
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 1-53 9.74e-28

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.


The actual alignment was detected with superfamily member cd14510:

Pssm-ID: 475123 [Multi-domain]  Cd Length: 177  Bit Score: 102.83  E-value: 9.74e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 427918117   1 MVCALLIASEIFLTAEESLYYFGERRTNKTHSNKFQGVETPSQNRYVGYFAQV 53
Cdd:cd14510  125 MVCAWLIYSGQFESAKEALEYFGERRTDKSVSSKFQGVETPSQSRYVGYFEKL 177
 
Name Accession Description Interval E-value
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
 62-192 2.68e-45

C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key form, of the PTEN protein, phosphatidyl-inositol triphosphate phosphatase, and it is the C-terminus. This domain may well include a CBR3 loop which means it plays a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc (pfam00782) suggesting that the C2 domain productively positions the catalytic part of the protein onto the membrane.


Pssm-ID: 463081  Cd Length: 133  Bit Score: 146.27  E-value: 2.68e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 427918117   62 PPRRILFIKRFIIYSI----RGDVCDLKVQVVMEKKVVFSStsLGNCSILHDIETDKILINVYDGPPLYDDVKVQFFSSN 137
Cdd:pfam10409   1 PPPKPLTLHSIILHGIpnfkSGGGCRPYIRIYQNKKKVFST--SGKYKKLKEYQQDDCVILFPKGIPVQGDVLVEFYHKG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 427918117  138 LPKYYDNCPFFFWFNTSFIQNNRLCLPRNELDNPHKQKAWKIYPPEFAVEILFGE 192
Cdd:pfam10409  79 SDLLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDKKDKRFPKDFKVELLFSE 133
PTP_VSP_TPTE cd14510
protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase ...
 1-53 9.74e-28

protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase/transmembrane phosphatase with tensin homology; Voltage-sensitive phosphatase (VSP) proteins comprise a family of phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. This family is conserved in deuterostomes; VSP was first identified as a sperm flagellar plasma membrane protein in Ciona intestinalis. Gene duplication events in primates resulted in the presence of paralogs, transmembrane phosphatase with tensin homology (TPTE) and TPTE2, that retain protein domain architecture but, in the case of TPTE, have lost catalytic activity. TPTE, also called cancer/testis antigen 44 (CT44), may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. TPTE2, also called TPTE and PTEN homologous inositol lipid phosphatase (TPIP), occurs in several differentially spliced forms; TPIP alpha displays phosphoinositide 3-phosphatase activity and is localized on the endoplasmic reticulum, while TPIP beta is cytosolic and lacks detectable phosphatase activity. VSP/TPTE proteins contain an N-terminal voltage sensor consisting of four transmembrane segments, a protein tyrosine phosphatase (PTP)-like phosphoinositide phosphatase catalytic domain, followed by a regulatory C2 domain.


Pssm-ID: 350360 [Multi-domain]  Cd Length: 177  Bit Score: 102.83  E-value: 9.74e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 427918117   1 MVCALLIASEIFLTAEESLYYFGERRTNKTHSNKFQGVETPSQNRYVGYFAQV 53
Cdd:cd14510  125 MVCAWLIYSGQFESAKEALEYFGERRTDKSVSSKFQGVETPSQSRYVGYFEKL 177
 
Name Accession Description Interval E-value
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
 62-192 2.68e-45

C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key form, of the PTEN protein, phosphatidyl-inositol triphosphate phosphatase, and it is the C-terminus. This domain may well include a CBR3 loop which means it plays a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc (pfam00782) suggesting that the C2 domain productively positions the catalytic part of the protein onto the membrane.


Pssm-ID: 463081  Cd Length: 133  Bit Score: 146.27  E-value: 2.68e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 427918117   62 PPRRILFIKRFIIYSI----RGDVCDLKVQVVMEKKVVFSStsLGNCSILHDIETDKILINVYDGPPLYDDVKVQFFSSN 137
Cdd:pfam10409   1 PPPKPLTLHSIILHGIpnfkSGGGCRPYIRIYQNKKKVFST--SGKYKKLKEYQQDDCVILFPKGIPVQGDVLVEFYHKG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 427918117  138 LPKYYDNCPFFFWFNTSFIQNNRLCLPRNELDNPHKQKAWKIYPPEFAVEILFGE 192
Cdd:pfam10409  79 SDLLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDKKDKRFPKDFKVELLFSE 133
PTP_VSP_TPTE cd14510
protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase ...
 1-53 9.74e-28

protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase/transmembrane phosphatase with tensin homology; Voltage-sensitive phosphatase (VSP) proteins comprise a family of phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. This family is conserved in deuterostomes; VSP was first identified as a sperm flagellar plasma membrane protein in Ciona intestinalis. Gene duplication events in primates resulted in the presence of paralogs, transmembrane phosphatase with tensin homology (TPTE) and TPTE2, that retain protein domain architecture but, in the case of TPTE, have lost catalytic activity. TPTE, also called cancer/testis antigen 44 (CT44), may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. TPTE2, also called TPTE and PTEN homologous inositol lipid phosphatase (TPIP), occurs in several differentially spliced forms; TPIP alpha displays phosphoinositide 3-phosphatase activity and is localized on the endoplasmic reticulum, while TPIP beta is cytosolic and lacks detectable phosphatase activity. VSP/TPTE proteins contain an N-terminal voltage sensor consisting of four transmembrane segments, a protein tyrosine phosphatase (PTP)-like phosphoinositide phosphatase catalytic domain, followed by a regulatory C2 domain.


Pssm-ID: 350360 [Multi-domain]  Cd Length: 177  Bit Score: 102.83  E-value: 9.74e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 427918117   1 MVCALLIASEIFLTAEESLYYFGERRTNKTHSNKFQGVETPSQNRYVGYFAQV 53
Cdd:cd14510  125 MVCAWLIYSGQFESAKEALEYFGERRTDKSVSSKFQGVETPSQSRYVGYFEKL 177
PTP_PTEN cd14509
protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; ...
 1-52 1.84e-10

protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; Phosphatase and tensin homolog (PTEN), also phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN or mutated in multiple advanced cancers 1 (MMAC1), is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It is a critical endogenous inhibitor of phosphoinositide signaling. It dephosphorylates phosphoinositide trisphosphate, and therefore, has the function of negatively regulating Akt. The PTEN/PI3K/AKT pathway regulates the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth. PTEN contains an N-terminal PIP-binding domain, a protein tyrosine phosphatase (PTP)-like catalytic domain, a regulatory C2 domain responsible for its cellular location, a C-tail containing phosphorylation sites, and a C-terminal PDZ domain.


Pssm-ID: 350359 [Multi-domain]  Cd Length: 158  Bit Score: 56.83  E-value: 1.84e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 427918117   1 MVCALLIASEIFLTAEESLYYFGERRTNkthsNKfQGVETPSQNRYVGYFAQ 52
Cdd:cd14509  111 MICCYLLYLGKFPSAKEALDFYGAKRTK----NK-KGVTIPSQRRYVYYYSR 157
PTP_PTEN-like cd14497
protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar ...
 1-50 2.28e-10

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.


Pssm-ID: 350347 [Multi-domain]  Cd Length: 160  Bit Score: 56.43  E-value: 2.28e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 427918117   1 MVCALLIASEIFLTAEESLYYFGERRTNKthsnKFQGVETPSQNRYVGYF 50
Cdd:cd14497  112 VICAYLLYYGQYSTADEALEYFAKKRFKE----GLPGVTIPSQLRYLQYF 157
PTP_auxilin-like cd14511
protein tyrosine phosphatase-like domain of auxilin and similar proteins; This subfamily ...
 1-53 1.03e-04

protein tyrosine phosphatase-like domain of auxilin and similar proteins; This subfamily contains proteins similar to auxilin, characterized by also containing a J domain. It includes auxilin, also called auxilin-1, and cyclin-G-associated kinase (GAK), also called auxilin-2. Auxilin-1 and -2 facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, while auxilin-1 which is nerve-specific. Both proteins contain a protein tyrosine phosphatase (PTP)-like domain similar to the PTP-like domain of PTEN (a phosphoinositide 3-phosphatase), and a C-terminal region with clathrin-binding and J domains. In addition, GAK contains an N-terminal protein kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2.


Pssm-ID: 350361 [Multi-domain]  Cd Length: 164  Bit Score: 40.80  E-value: 1.03e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 427918117   1 MVCALLIASEIFLTAEESLYYFGERRTnkthsnkfQGVETPSQNRYVGYFAQV 53
Cdd:cd14511  120 VVCALLVYCGLFKTPEDALQMFAVKRC--------PPGLSPSELRYLYYFSDI 164
PTP_tensin cd14508
protein tyrosine phosphatase-like domain of tensins; The tensin family of intracellular ...
 2-51 1.98e-03

protein tyrosine phosphatase-like domain of tensins; The tensin family of intracellular proteins (tensin-1, -2, -3 and -4) act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of tensin expression has been implicated in human cancer. Tensin-1, -2, and -3 contain an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. In addition, tensin-2 contains a zinc finger N-terminal to its PTP domain. Tensin-4 is not included in this model as it does not contain a PTP-like domain.


Pssm-ID: 350358 [Multi-domain]  Cd Length: 159  Bit Score: 37.37  E-value: 1.98e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 427918117   2 VCALLIASEIFLTAEESLYYFGERRTnktHSNKFQGVETPSQNRYVGYFA 51
Cdd:cd14508  111 VSAYMHYSKISATADQALDRFAMKRF---YDDKVGPLGQPSQKRYVGYFS 157
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH