in StAR and phosphatidylcholine transfer protein; putative lipid-binding domain in StAR and phosphatidylcholine transfer protein

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462600559   24 IEEDKW--RVAKKTKDVTVWRKPSEEFNGYLYKAQGVID----DLVYSIIDHIRPgpcRLDWDSLMTSLDILENFEENCC 97
Cdd:smart00234  15 ASEEGWvlSSENENGDEVRSIFSPGRKPGEAFRLVGVVPmvcaDLVEELMDDLEY---RPEWDKNVAKAETLEVIDNGTV 91

                           90       100
                   ....*....|....*....|....*
gi 2462600559   98 VMRYTTAGQlWNIISPREFVDFSYT 122
Cdd:smart00234  92 IYHYVSKFA-AGPVSPRDFVFVRYW 115

Lipid-binding START domain of mammalian STARD4, -5, -6, and related proteins; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD4, -5, and -6. The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD4 plays an important role in steroidogenesis, trafficking cholesterol into mitochondria. It specifically binds cholesterol, and demonstrates limited binding to another sterol, 7a-hydroxycholesterol. STARD4 and STARD5 are ubiquitously expressed, with highest levels in liver and kidney. STRAD5 functions in the kidney within the proximal tubule cells where it is associated with the Endoplasmic Reticulum (ER), and may participate in ER-associated cholesterol transport. It binds cholesterol and 25-hydroxycholesterol. Expression of the gene encoding STARD5 is increased by ER stress, and its mRNA and protein levels are elevated in a type I diabetic mouse model of human diabetic nephropathy. STARD6 is expressed in male germ cells of normal rats, and in the steroidogenic Leydig cells of perinatal hypothyroid testes. It may play a pivotal role in the steroidogenesis as well as in the spermatogenesis of normal rats. STARD6 has also been detected in the rat nervous system, and may participate in neurosteroid synthesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462600559   5 SDVASFATKLKNTLIQYHSIEeDKWRVAKKTKDVTVWRKPSEEFNGYLYKAQGVIDDLVYSIIDHIRP--GPCRLDWDSL 82
Cdd:cd08867     1 MDFKVIAEKLANEALQYINDT-DGWKVLKTVKNITVSWKPSTEFTGHLYRAEGIVDALPEKVIDVIIPpcGGLRLKWDKS 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462600559  83 MTSLDILENFEENCCVMRYTTAGQLWNIISPREFVDFSYTVGYKEGLLSCAST 135
Cdd:cd08867    80 LKHYEVLEKISEDLCVGRTITPSAAMGLISPRDFVDLVYVKRYEDNQWSSSGK 132

Lipid-binding START domain of mammalian STARD1-STARD15 and related proteins; This family includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD1-STARD15, and related domains, such as the START domain of the Arabidopsis homeobox protein GLABRA 2. The mammalian STARDs are grouped into 8 subfamilies. This family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. For some members of this family, specific lipids that bind in this pocket are known; these include cholesterol (STARD1/STARD3/ STARD4/STARD5), 25-hydroxycholesterol (STARD5), phosphatidylcholine (STARD2/ STARD7/STARD10), phosphatidylethanolamine (STARD10) and ceramides (STARD11). The START domain is found either alone or in association with other domains. Mammalian STARDs participate in the control of various cellular processes including lipid trafficking between intracellular compartments, lipid metabolism, and modulation of signaling events. Mutation or altered expression of STARDs is linked to diseases such as cancer, genetic disorders, and autoimmune disease. The Arabidopsis homeobox protein GLABRA 2 suppresses root hair formation in hairless epidermal root cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462600559  25 EEDKWRVAKKTKDVTVWRKPSEEFNGYLYKAQGVIDDLVYSIIDHIRPGPCRLDWDSLMTSLDILENFEENCCVMRYTTA 104
Cdd:cd00177    13 EPEGWKLVKEKDGVKIYTKPYEDSGLKLLKAEGVIPASPEQVFELLMDIDLRKKWDKNFEEFEVIEEIDEHTDIIYYKTK 92

                          90       100
                  ....*....|....*....|....
gi 2462600559 105 GQLwnIISPREFVDFSYTVGYKEG 128
Cdd:cd00177    93 PPW--PVSPRDFVYLRRRRKLDDG 114

Cholesterol-binding START domain of mammalian STARD1, -3 and related proteins; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of STARD1 (also known as StAR) and STARD3 (also known as metastatic lymph node 64/MLN64). The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. This STARD1-like subfamily has a high affinity for cholesterol. STARD1/StAR can reduce macrophage lipid content and inflammatory status. It plays an essential role in steroidogenic tissues: transferring the steroid precursor, cholesterol, from the outer to the inner mitochondrial membrane, across the aqueous space. Mutations in the gene encoding STARD1/StAR can cause lipid congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by a steroid synthesis deficiency and an accumulation of cholesterol in the adrenal glands and the gonads. STARD3 may function in trafficking endosomal cholesterol to a cytosolic acceptor or membrane. In addition to having a cytoplasmic START cholesterol-binding domain, STARD3 also contains an N-terminal MENTAL cholesterol-binding and protein-protein interaction domain. The MENTAL domain contains transmembrane helices and anchors MLN64 to endosome membranes. The gene encoding STARD3 is overexpressed in about 25% of breast cancers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462600559  10 FATKLKNTLIQYHSIEEDK-WRVAKKTKDVTVWRKPSEEFNGYLYKAQGVID----DLVYSIIDHIRPGPcrlDWDSLMT 84
Cdd:cd08868     6 YLKQGAEALARAWSILTDPgWKLEKNTTWGDVVYSRNVPGVGKVFRLTGVLDcpaeFLYNELVLNVESLP---SWNPTVL 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2462600559  85 SLDILENFEENCCVMRYTTAGQLWNIISPREFVDFSYTvGYKEG--LLSCASTK 136
Cdd:cd08868    83 ECKIIQVIDDNTDISYQVAAEAGGGLVSPRDFVSLRHW-GIRENcyLSSGVSVE 135

START domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462600559  25 EEDKWRVAKKTKDVTVWRKPSEEFNGYLYKAQGVID----DLVYSIIDHirpGPCRLDWDSLMTSLDILENFEENCCVMR 100
Cdd:pfam01852  17 DEPGWVLLSSNENGDVVLQIVEPDHGEASRASGVVPmvaaLLVAELLKD---MEYRAQWDKDVRSAETLEVISSGGDLQY 93

                          90       100
                  ....*....|....*....|.
gi 2462600559 101 YTTAGQLWNIISPREFVDFSY 121
Cdd:pfam01852  94 YVAALVAPSPLSPRDFVFLRY 114