1UW5,1KCM,1T27,2A1L


Conserved Protein Domain Family
SRPBCC_PITPNA-B_like

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cd08888: SRPBCC_PITPNA-B_like 
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Lipid-binding SRPBCC domain of mammalian PITPNA, -B, and related proteins (Class I PITPs)
This subgroup includes the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain of mammalian Class 1 phosphatidylinositol transfer proteins (PITPs), PITPNA/PITPalpha and PITPNB/PITPbeta, Drosophila vibrator, and related proteins. These are single domain proteins belonging to the PITP family of lipid transfer proteins, and to the SRPBCC domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. In vitro, PITPs bind phosphatidylinositol (PtdIns), as well as phosphatidylcholine (PtdCho) but with a lower affinity. They transfer these lipids from one membrane compartment to another. The cellular roles of PITPs include inositol lipid signaling, PtdIns metabolism, and membrane trafficking. In addition, PITPNB transfers sphingomyelin in vitro, with a low affinity. PITPNA is found chiefly in the nucleus and cytoplasm; it is enriched in the brain and predominantly localized in the axons. A reduced expression of PITPNA contributes to the neurodegenerative phenotype of the mouse vibrator mutation. The role of PITPNA in vivo may be to provide PtdIns for localized PI3K-dependent signaling, thereby controlling the polarized extension of axonal processes. PITPNA homozygous null mice die soon after birth from complicated organ failure, including intestinal and hepatic steatosis, hypoglycemia, and spinocerebellar disease. PITPNB is associated with the Golgi and ER, and is highly expressed in the liver. Deletion of the PITPNB gene results in embryonic lethality. The PtdIns and PtdCho exchange activity of PITPNB is required for COPI-mediated retrograde transport from the Golgi to the ER. Drosophila vibrator localizes to the ER, and has an essential role in cytokinesis during mitosis and meiosis.
Statistics
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PSSM-Id: 176897
View PSSM: cd08888
Aligned: 14 rows
Threshold Bit Score: 439.953
Threshold Setting Gi: 66804251
Created: 29-Jul-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 38 residues -Click on image for an interactive view with Cn3D
Feature 1:lipid binding site [chemical binding site]
Evidence:
  • Comment:This phospholipid binding site is comprised of a lipid-headgroup binding pocket and two hydrophobic channels which accommodate the acyl chains.
  • Comment:There are subtle differences in the orientation of PtdCho acyl chains, when this lipid is bound to the different PTIP isoforms.
  • Structure:1UW5_A; human PITPNA bound with PtdIns, contacts at 4A
    View structure with Cn3D
  • Structure:1T27_A; human PITPNA bound with 1,2-dioleoyl-PtdCho, contacts at 4A
    View structure with Cn3D
  • Structure:2AIL_A; Rattus norvegicus PITPNB bound with 1,2-dioleoyl-PtdCho, contacts at 4A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                           ##  #   #  #      #                               # # # #  # 
1UW5_A         3 LLKEYRVILPVSVDEYQVGQLYSVAEASKNETGGGEGVEVLVNEPYEkd--------------geKGQYTHKIYHLQSKV 68  human
1T27_A         3 LLKEYRVILPVSVDEYQVGQLYSVAEASKNETGGGEGVEVLVNEPYEkdd-------------geKGQYTHKIYHLQSKV 69  Norway rat
2A1L_A         2 LIKEFRVVLPCSVQEYQVGQLYSVAEASKNETGGGEGIEVLKNEPYEnd--------------geKGQYTHKIYHLKSKV 67  Norway rat
NP_957229      2 LIKEFRIVLPVSVEEYQVGQLYSVAEASKNETGGGDGVEVLKNEPYEked-------------geKGQYTHKIYRLQSKV 68  zebrafish
NP_001086964   3 LIKEFRIVLPCSVEEYQVGQLYSVAEASKNETGGGEGIEVLKNEPYEkd--------------geKGQYTHKIYHLKSKV 68  African clawed ...
NP_001034355   3 LIKEFRVVLPCSVQEYQVGQLYSVAEASKNETGGGEGIQVLINEPYEkd--------------deKGQYTHKIYHLKSKV 68  chicken
NP_524404      2 QIKEFRVTLPLTVEEYQVAQLFSVAEASKENTGGGEGIEVLKNEPFEdfpll--------ggkynSGQYTYKIYHLQSKV 73  fruit fly
XP_001635342   3 VIKEYRIPLPISVEEYQIAQLYAVAEASKNETGGGEGIEVLVNEPYTagegghg----knmppgmDGQYTHKLIHLHSKV 78  starlet sea ane...
CAZ30613       2 IVKEYRVILPMTVEEYQVGQLYSVAETSKGETGGGDGVQILVNEPFDqttykpdrpllkgdprftTGQYTHKYYHLAQKV 81  Schistosoma man...
XP_002128690   2 IIKEYRVILPMTVEEYQVAQLWSVAEASKNETGGGEGIEVLNNEPYTktlen---------gtveSGQYTNKIYHFASRV 72  Ciona intestinalis
Feature 1        #  #   #   ## # # # #    # # #  # ##     # #                                    
1UW5_A        69 PTFVRXLAPEGALNIHEKAWNAYPYCRTVIt-NEYXKEDFLIKIETWHKPDLGT-QENVHKLEPEAWKHVEAVYIDIADR 146 human
1T27_A        70 PTFVRMLAPEGALNIHEKAWNAYPYCRTVIt-NEYMKEDFLIKIETWHKPDLGT-QENVHKLEPEAWKHVEAIYIDIADR 147 Norway rat
2A1L_A        68 PAFVRMIAPEGSLVFHEKAWNAYPYCRTIVt-NEYMKDDFFIKIETWHKPDLGT-LENVHGLDPNTWKTVEIVHIDIADR 145 Norway rat
NP_957229     69 PSFVRLLAPSSALIIHEKAWNAYPYCRTVLt-NEYMKDNFLIMIETWHKPDLGE-QENVHNLDSERWKQVEVIHIDIADR 146 zebrafish
NP_001086964  69 PGFVKMFAPEGSLVFHEKAWNAFPYCRTIVt-NEYMKDDFFIKIETWHKPDMGT-QENVHCLDPNIWKSVDVVDIDIADR 146 African clawed ...
NP_001034355  69 PGFVRMIAPEGSLVFHEKAWNAYPYCRTIVt-NEYMKDDFFIKIETWHKPDLGT-SENVHNLDPNTWKSVEVVHIDIADR 146 chicken
NP_524404     74 PAYIRLLAPKGSLEIHEEAWNAYPYCRTIItnPKFMKDAFKIIIDTLHVGDAGD-SENVHELTPDKLKVREIVHIDIAND 152 fruit fly
XP_001635342  79 PSFVRMLAPSGSLEVHEKAWNAYPFCRTEYs-NTYMKEHFSVIIDTWHKPGHKDeFHNVHNLGNPELQKREIVNIDIVND 157 starlet sea ane...
CAZ30613      82 PGFLRVIAPESAFVFNEYAWNAYPYCRTIIt-NNYMMEKFSVTIESLHMDSLIN-VENAHQLSPEKWAEVEVIYIDIGDI 159 Schistosoma man...
XP_002128690  73 PGFIRLFAPTGSLSAKEEAWNAYPSCRTEFtnPGYMKDNFQIVIQSYHADDVGE-SENVHNLTPKQLKDREVITIDIAND 151 Ciona intestinalis
Feature 1                                                                    #     # #         # 
1UW5_A       147 SqvlSKDYKAEEDPAKFKSIKTGRGPLGPNWKQELvnq-------------kdCPYXCAYKLVTVKFKWWGLQNKVENFI 213 human
1T27_A       148 SqvlSKDYKAEEDPAKFKSIKTGRGPLGPNWKQELvnq-------------kdCPYMCAYKLVTVKFKWWGLQNKVENFI 214 Norway rat
2A1L_A       146 SqvePADYKADEDPALFQSVKTKRGPLGPNWKKELant-------------pdCPKMCAYKLVTIKFKWWGLQSKVENFI 212 Norway rat
NP_957229    147 SqvdTKDYKPDEDPATFKSQKTGRGPLGPDWKKELpqk-------------kdCPHMCAYKLVTVNFKWFGLQKKVEGFI 213 zebrafish
NP_001086964 147 SqvePADYKATEDPAIFQSVKTKRGPLGPNWKKELvna-------------edCPRMCAYKLVTIKFKWWGLQNKIESFI 213 African clawed ...
NP_001034355 147 TqvePGDYKADEDPALFQSVKTKRGPLGPNWKKELatd-------------eeCPKMCAYKLVTIKFKWWGLQNKVENLI 213 chicken
NP_524404    153 Pv-lPADYKPDEDPTTYQSKKTGRGPLVGSDWKKHv-----------------NPVMTCYKLVTCEFKWFGLQTRVENFI 214 fruit fly
XP_001635342 158 Kv-dPHEYKADEDPSKVGSEKAKRGPLKKDWQQKNeedps--------kskegYPMMTCYKLYRVEFKWWGLQTKVESII 228 starlet sea ane...
CAZ30613     160 Sq-aGKDYNPNEDPTTFRSEKTGRGPLKPKWWENGy----------------kGPIMCAYKLVSCEFKVWGMQGRIEKMI 222 Schistosoma man...
XP_002128690 152 Vv-rSADYKPEFDPSKFTSQKAGRGPFGPNWIEHMrmqkqiydnqepgagiqrPAVMCAYKLVTVKFKWLGFQNRIEKFI 230 Ciona intestinalis
Feature 1          ## ###  #                                   
1UW5_A       214 HKQERRLFTNFHRQLFCWLDKWVDLTXDDIRRXEEETKRQLDEXRQ 259 human
1T27_A       215 HKQEKRLFTNFHRQLFCWLDKWVDLTMDDIRRMEEETKRQLDEMRQ 260 Norway rat
2A1L_A       213 QKQEKRIFTNLHRQLFCWIDKWIDLTMEDIRRMEDETQKELETMRK 258 Norway rat
NP_957229    214 HRQEKRLFTSFHRQLFCWLDRWIDLTMEDIRRMEEETQKELDKMRE 259 zebrafish
NP_001086964 214 QKQEKRIFTNFHRQVFCWIDDWIDLTMEDIRRMEDKTQRELEAMRK 259 African clawed frog
NP_001034355 214 QKQEKRIFTNFHRQLFCWIDKWIDLTMEDIRRMEDETQKELEALRN 259 chicken
NP_524404    215 QKSERRLFTNFHRQVFCSTDRWYGLTMEDIRAIEDQTKEELDKARQ 260 fruit fly
XP_001635342 229 MKAVHRLLRNFHRQMFCWMDRWFGMTMDDIRRIEDKTKKELDEMRH 274 starlet sea anemone
CAZ30613     223 QRQERRLFANFHRQVFCWMDKWHGWTMEDVRLHEEQTKKELEEVRF 268 Schistosoma mansoni
XP_002128690 231 HNQERRLFTNFHRQVVCWMDNYHGLTMVDIRRIEDEIKKELDRIRE 276 Ciona intestinalis

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