ASAH2_HUMAN » Neutral ceramidase

ASAH2_HUMAN » Neutral ceramidase
Magnify ASAH2_HUMAN » Neutral ceramidaseEnlarged view of image
3D view in GLMol or JMol

gray dot

Download Coordinates

gray dot

Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
ASAH2_HUMAN » Neutral ceramidase » N-CDase; NCDase; Acylsphingosine deacylase 2;BCDase;LCDase;hCD; N-acylsphingosine amidohydrolase 2;Non-lysosomal ceramidase;
Hydrophobic Thickness 35.2 ± 4.4 Å
Tilt Angle 43 ± 11°
ΔGtransfer -33.3 kcal/mol
ΔGfold -26.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology In
TM Segments 8-37 (8-42)
Pathways

ceramide degradation (BioCyc)

Sphingolipid metabolism (KEGG)

sphingosine and sphingosine-1-phosphate metabolism (BioCyc)

PDB none
OPM 4wgk
Complexes none
Interactions none
Domains

AA: 102-608, PDBID: 4WGK, Subunit A, Seq Identity:100%, Neutral/alkaline non-lysosomal ceramidase, N-terminal

AA: 610-777, PDBID: 4WGK, Subunit A, Seq Identity:100%, Neutral/alkaline non-lysosomal ceramidase, C-terminal

UniProt annotation for ASAH2_HUMAN » Neutral ceramidase
FUNCTION: Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid at an optimal pH of 6.5-8.5. Acts as a key regulator of sphingolipid signaling metabolites by generating sphingosine at the cell surface. Acts as a repressor of apoptosis both by reducing C16-ceramide, thereby preventing ceramide-induced apoptosis, and generating sphingosine, a precursor of the antiapoptotic factor sphingosine 1-phosphate. Probably involved in the digestion of dietary sphingolipids in intestine by acting as a key enzyme for the catabolism of dietary sphingolipids and regulating the levels of bioactive sphingolipid metabolites in the intestinal tract.

CATALYTIC ACTIVITY: N-acylsphingosine + H(2)O = a carboxylate + sphingosine.

ENZYME REGULATION: Inhibited by dithiothreitol (DTT), 2- mercaptoethanol, Zn(2+), Cu(2+) and Fe(2+). Enhanced by Na(+) and Ca(2+), and at lower level Mg(2+) and Mn(2+).

TISSUE SPECIFICITY: Primarily expressed in the intestine (PubMed). Ubiquitously expressed with higher levels in kidney, skeletal muscle and heart (PubMed). According to PubMed:17334805, ubiquitous expression attributed to ASAH2 may be actually that of the paralog ASAH2B.

UniProt features for ASAH2_HUMAN » Neutral ceramidase
CHAIN 1 780 Neutral ceramidase.
CHAIN 99 780 Neutral ceramidase soluble form (By similarity).
REGION 770 780 Required for correct folding and localization (By similarity).
ACT_SITE 354 354 Nucleophile.
Amino Acid Sequence for ASAH2_HUMAN » Neutral ceramidase
MAKRTFSNLE TFLIFLLVMM SAITVALLSL LFITSGTIEN HKDLGGHFFS TTQSPPATQG STAAQRSTAT QHSTATQSST ATQTSPVPLT PESPLFQNFS GYHIGVGRAD CTGQVADINL MGYGKSGQNA QGILTRLYSR AFIMAEPDGS NRTVFVSIDI GMVSQRLRLE VLNRLQSKYG SLYRRDNVIL SGTHTHSGPA GYFQYTVFVI ASEGFSNQTF QHMVTGILKS IDIAHTNMKP GKIFINKGNV DGVQINRSPY SYLQNPQSER ARYSSNTDKE MIVLKMVDLN GDDLGLISWF AIHPVSMNNS NHLVNSDNVG YASYLLEQEK NKGYLPGQGP FVAAFASSNL GDVSPNILGP RCINTGESCD NANSTCPIGG PSMCIAKGPG QDMFDSTQII GRAMYQRAKE LYASASQEVT GPLASAHQWV DMTDVTVWLN STHASKTCKP ALGYSFAAGT IDGVGGLNFT QGKTEGDPFW DTIRDQILGK PSEEIKECHK PKPILLHTGE LSKPHPWHPD IVDVQIITLG SLAITAIPGE FTTMSGRRLR EAVQAEFASH GMQNMTVVIS GLCNVYTHYI TTYEEYQAQR YEAASTIYGP HTLSAYIQLF RNLAKAIATD TVANLSRGPE PPFFKQLIVP LIPSIVDRAP KGRTFGDVLQ PAKPEYRVGE VAEVIFVGAN PKNSVQNQTH QTFLTVEKYE ATSTSWQIVC NDASWETRFY WHKGLLGLSN ATVEWHIPDT AQPGIYRIRY FGHNRKQDIL KPAVILSFEG TSPAFEVVTI