START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily; SRPBCC domains have a deep hydrophobic ligand-binding pocket; they bind diverse ligands. Included in this superfamily are the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD1-STARD15, and the C-terminal catalytic domains of the alpha oxygenase subunit of Rieske-type non-heme iron aromatic ring-hydroxylating oxygenases (RHOs_alpha_C), as well as the SRPBCC domains of phosphatidylinositol transfer proteins (PITPs), Bet v 1 (the major pollen allergen of white birch, Betula verrucosa), CoxG, CalC, and related proteins. Other members of this superfamily include PYR/PYL/RCAR plant proteins, the aromatase/cyclase (ARO/CYC) domains of proteins such as Streptomyces glaucescens tetracenomycin, and the SRPBCC domains of Streptococcus mutans Smu.440 and related proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26346204   1 MKLISPRDFVDLVLVKKYEDGTISSNATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGDPNKTNLVTFFQTDLSGYLPQS 80
Cdd:cd08903 105 MKIISPRDFVDVVLVKRYEDGTISSNATNVEHPLCPPQAGFVRGFNHPCGCFCEPVPGEPDKTQLVSFFQTDLSGYLPQT 184

                        90       100
                ....*....|....*....|....
gi 26346204  81 VVDSFFPRSMAEFYPNLQKAVRKF 104
Cdd:cd08903 185 VVDSFFPASMAEFYNNLTKAVKAL 208

Lipid-binding START domain of mammalian STARD5 and related proteins; This subgroup includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD5, and related domains. It belongs to the START domain family, and in turn 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. STARD5 is ubiquitously expressed, with highest levels in liver and kidney. STARD5 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26346204   1 MKLISPRDFVDLVLVKKYEDGTISSNATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGDPNKTNLVTFFQTDLSGYLPQS 80
Cdd:cd08903 105 MKIISPRDFVDVVLVKRYEDGTISSNATNVEHPLCPPQAGFVRGFNHPCGCFCEPVPGEPDKTQLVSFFQTDLSGYLPQT 184

                        90       100
                ....*....|....*....|....
gi 26346204  81 VVDSFFPRSMAEFYPNLQKAVRKF 104
Cdd:cd08903 185 VVDSFFPASMAEFYNNLTKAVKAL 208

START domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26346204     4 ISPRDFVDLVLVKKYEDG--TISSNAthVEHPLCPPKPGFVRGFNHPCGCFCEPLPGdpNKTNLVTFFQTDLSGYLPQSV 81
Cdd:pfam01852 104 LSPRDFVFLRYWRRLGGGvyVIVDRS--VTHPQFPPSSGYVRAERLPSGYLIQPCGN--GPSKVTWVSHADLKGWLPSWL 179

                          90
                  ....*....|..
gi 26346204    82 VDSFFPRSMAEF 93
Cdd:pfam01852 180 LRSLYKSGMPEG 191

Lipid-binding START domain of mammalian STARD5 and related proteins; This subgroup includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD5, and related domains. It belongs to the START domain family, and in turn 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. STARD5 is ubiquitously expressed, with highest levels in liver and kidney. STARD5 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26346204   1 MKLISPRDFVDLVLVKKYEDGTISSNATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGDPNKTNLVTFFQTDLSGYLPQS 80
Cdd:cd08903 105 MKIISPRDFVDVVLVKRYEDGTISSNATNVEHPLCPPQAGFVRGFNHPCGCFCEPVPGEPDKTQLVSFFQTDLSGYLPQT 184

                        90       100
                ....*....|....*....|....
gi 26346204  81 VVDSFFPRSMAEFYPNLQKAVRKF 104
Cdd:cd08903 185 VVDSFFPASMAEFYNNLTKAVKAL 208

Lipid-binding START domain of mammalian STARD6 and related proteins; This subgroup includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD6 and related domains. It belongs to the START domain family, and in turn 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. 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 26346204   1 MKLISPRDFVDLVLVKKYEDGTISSNATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGDPNKTNLVTFFQTDLSGYLPQS 80
Cdd:cd08904 103 MGSISPRDFVDLVHIKRYEGNMNIVSSVSVEYPQCPPSSNYIRGYNHPCGYVCSPLPENPAYSKLVMFVQPELRGNLSRS 182

                        90       100
                ....*....|....*....|..
gi 26346204  81 VVDSFFPRSMAEFYPNLQKAVR 102
Cdd:cd08904 183 VIEKTMPTNLVNLILDAKDGIK 204

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 26346204   3 LISPRDFVDLVLVKKYEDGTISSnATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGDPNKTNLVTFFQTDLSGYLPQSVV 82
Cdd:cd08868 108 LVSPRDFVSLRHWGIRENCYLSS-GVSVEHPAMPPTKNYVRGENGPGCWILRPLPNNPNKCNFTWLLNTDLKGWLPQYLV 186

                        90
                ....*....|....*..
gi 26346204  83 DSFFPRSMAEFYPNLQK 99
Cdd:cd08868 187 DQALASVLLDFMKHLRK 203

Cholesterol-binding START domain of mammalian STARD1 and related proteins; This subgroup includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of STARD1 (also known as StAR) and related proteins. It belongs to the START domain family, and in turn 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. STARD1 has a high affinity for cholesterol. It 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26346204   3 LISPRDFVDlVLVKKYEDGTISSNATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGDPNKTNLVTFFQTDLSGYLPQSVV 82
Cdd:cd08905 109 VVGPRDFVS-VRCAKRRGSTCVLAGMATHFGLMPEQKGFIRAENGPTCIVLRPLAGDPSKTKLTWLLSIDLKGWLPKSII 187

                        90
                ....*....|....*..
gi 26346204  83 DSFFPRSMAEFYPNLQK 99
Cdd:cd08905 188 NQVLSQTQVDFANHLRQ 204

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 26346204      1 MKLISPRDFVDLVLVKKYEDGTISSNATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGdpNKTNLVTFFQTDLSGYLPQS 80
Cdd:smart00234 101 AGPVSPRDFVFVRYWREDEDGSYAVVDVSVTHPTSPPESGYVRAENLPSGLLIEPLGN--GPSKVTWVSHADLKGWLPHW 178

                           90       100
                   ....*....|....*....|...
gi 26346204     81 VVDSFFPRSMAEFYPNLQKAVRK 103
Cdd:smart00234 179 LVRSLIKSGLAEFAKTLVATLQK 201

Lipid-binding START domain of mammalian STARD10 and related proteins; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD10 (also known as CGI-52, PTCP-like, and SDCCAG28). 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. STARD10 binds phophatidylcholine and phosphatidylethanolamine. This protein is widely expressed and is synthesized constitutively in many organs. It may function in the liver in the export of phospholipids into bile. It is concentrated in the sperm flagellum, and may play a role in energy metabolism. In the mammary gland it may participate in the enrichment of lipids in milk, and be a potential marker of differentiation. Its expression is induced in this gland during gestation and lactation. It is overexpressed in mammary tumors from Neu/ErbB2 transgenic mice, in several breast carcinoma cell lines, and in 35% of primary human breast cancers, and may cooperate with c-erbB receptor signaling in breast oncogenesis. It is a potential marker of disease outcome in breast cancer; loss of STARD10 expression in breast cancer strongly predicts an aggressive disease course. The lipid transfer activity of STRAD10 is downregulated by phosphorylation of its Ser284 by CK2 (casein kinase 2).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26346204   4 ISPRDFVDLVLVKKYEDGTISSNaTHVEHPLCPPKPGFVRGFNHPCGCFCEPLPgdPNKTNLVTFFQTDLSGYLPQSVVD 83
Cdd:cd08871 106 LKNRDFVNLRSWLEFGGEYIIFN-HSVKHKKYPPRKGFVRAISLLTGYLIRPTG--PKGCTLTYVTQNDPKGSLPKWVVN 182

                        90       100
                ....*....|....*....|....*
gi 26346204  84 S----FFPRSMAefypNLQKAVRKF 104
Cdd:cd08871 183 KattkLAPKVMK----KLHKAALKY 203

Protein of unknown function (DUF3074); This eukaryotic family of proteins has no known function but appears to be part of the START superfamily.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 26346204     2 KLISPRDFVDLVLVKKYEDGTISSNATH---------VEHPLCPPKPGFVRG 44
Cdd:pfam11274  68 GPLTPRDFVVLLLTADLPPEESPGSEHAefmvvsipvDDHPDAPPRKGFVRG 119