Q6PIU2 (NCEH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neutral cholesterol ester hydrolase 1
Short name=NCEH
EC=3.1.1.-

Alternative name(s):
Arylacetamide deacetylase-like 1

Gene names

Name:	NCEH1
Synonyms:	AADACL1, KIAA1363

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	408 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolyzes 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor. May be responsible for cholesterol ester hydrolysis in macrophages, thereby contributing to the development of atherosclerosis. Also involved in organ detoxification by hydrolyzing exogenous organophosphorus compounds. May contribute to cancer pathogenesis by promoting tumor cell migration. Ref.5
Subcellular location	Membrane; Single-pass type II membrane protein Probable. Microsome By similarity Ref.4.
Tissue specificity	Expressed in monocyte-derived macrophages. Up-regulated in invasive melanoma and breast carcinoma cell lines. Ref.4 Ref.6
Post-translational modification	N-glycosylated. Ref.4
Sequence similarities	Belongs to the 'GDXG' lipolytic enzyme family.
Sequence caution	The sequence AAH28734.2 differs from that shown. Reason: Erroneous initiation. The sequence AAH47588.2 differs from that shown. Reason: Erroneous initiation. The sequence BAA92601.1 differs from that shown. Reason: Erroneous initiation. The sequence BAH13028.1 differs from that shown. Reason: Erroneous initiation. The sequence BAH14142.1 differs from that shown. Reason: Erroneous initiation. The sequence BAH14802.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	carboxylesterase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6PIU2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6PIU2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     123-123: K → SASWSPSDE

Isoform 3 (identifier: Q6PIU2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-133: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 408	408	Neutral cholesterol ester hydrolase 1		PRO_0000265939
Regions
	Topological domain	1 – 4	4	Cytoplasmic Potential
	Transmembrane	5 – 25	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	26 – 408	383	Lumenal Potential
Sites
	Active site	191	1	By similarity
	Active site	348	1	By similarity
	Active site	378	1	By similarity
Amino acid modifications
	Glycosylation	270	1	N-linked (GlcNAc...) Potential
	Glycosylation	287	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	389	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 133	133	Missing in isoform 3.		VSP_037518
	Alternative sequence	123	1	K → SASWSPSDE in isoform 2.		VSP_037519
	Natural variant	19	1	V → F. Corresponds to variant rs35316420 [ dbSNP | Ensembl ].		VAR_047099
	Natural variant	71	1	K → Q. Corresponds to variant rs2302815 [ dbSNP | Ensembl ].		VAR_047100
	Natural variant	343	1	L → M. Ref.3 Corresponds to variant rs17857335 [ dbSNP | Ensembl ].		VAR_047101
Experimental info
	Sequence conflict	16	1	A → T in BAA92601. Ref.1
	Sequence conflict	58	1	H → R in BAH13028. Ref.2
	Sequence conflict	72	1	K → R in BAH14802. Ref.2
	Sequence conflict	79	1	Q → K in AAH47588. Ref.3
	Sequence conflict	254	1	D → G in BAH14142. Ref.2
	Sequence conflict	329	1	A → S in BAH14142. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 12, 2006. Version 3. Checksum: E5754850BE9805B5	FASTA	408	45,808
	10 20 30 40 50 60 MRSSCVLLTA LVALAAYYVY IPLPGSVSDP WKLMLLDATF RGAQQVSNLI HYLGLSHHLL 70 80 90 100 110 120 ALNFIIVSFG KKSAWSSAQV KVTDTDFDGV EVRVFEGPPK PEEPLKRSVV YIHGGGWALA 130 140 150 160 170 180 SAKIRYYDEL CTAMAEELNA VIVSIEYRLV PKVYFPEQIH DVVRATKYFL KPEVLQKYMV 190 200 210 220 230 240 DPGRICISGD SAGGNLAAAL GQQFTQDASL KNKLKLQALI YPVLQALDFN TPSYQQNVNT 250 260 270 280 290 300 PILPRYVMVK YWVDYFKGNY DFVQAMIVNN HTSLDVEEAA AVRARLNWTS LLPASFTKNY 310 320 330 340 350 360 KPVVQTTGNA RIVQELPQLL DARSAPLIAD QAVLQLLPKT YILTCEHDVL RDDGIMYAKR 370 380 390 400 LESAGVEVTL DHFEDGFHGC MIFTSWPTNF SVGIRTRNSY IKWLDQNL
	Isoform 2 [UniParc]. Checksum: A315923F59D660E7	FASTA	416	46,627
	10 20 30 40 50 60 MRSSCVLLTA LVALAAYYVY IPLPGSVSDP WKLMLLDATF RGAQQVSNLI HYLGLSHHLL 70 80 90 100 110 120 ALNFIIVSFG KKSAWSSAQV KVTDTDFDGV EVRVFEGPPK PEEPLKRSVV YIHGGGWALA 130 140 150 160 170 180 SASASWSPSD EIRYYDELCT AMAEELNAVI VSIEYRLVPK VYFPEQIHDV VRATKYFLKP 190 200 210 220 230 240 EVLQKYMVDP GRICISGDSA GGNLAAALGQ QFTQDASLKN KLKLQALIYP VLQALDFNTP 250 260 270 280 290 300 SYQQNVNTPI LPRYVMVKYW VDYFKGNYDF VQAMIVNNHT SLDVEEAAAV RARLNWTSLL 310 320 330 340 350 360 PASFTKNYKP VVQTTGNARI VQELPQLLDA RSAPLIADQA VLQLLPKTYI LTCEHDVLRD 370 380 390 400 410 DGIMYAKRLE SAGVEVTLDH FEDGFHGCMI FTSWPTNFSV GIRTRNSYIK WLDQNL
	Isoform 3 [UniParc]. Checksum: 1D5212243D62F48B	FASTA	275	31,168
	10 20 30 40 50 60 MAEELNAVIV SIEYRLVPKV YFPEQIHDVV RATKYFLKPE VLQKYMVDPG RICISGDSAG 70 80 90 100 110 120 GNLAAALGQQ FTQDASLKNK LKLQALIYPV LQALDFNTPS YQQNVNTPIL PRYVMVKYWV 130 140 150 160 170 180 DYFKGNYDFV QAMIVNNHTS LDVEEAAAVR ARLNWTSLLP ASFTKNYKPV VQTTGNARIV 190 200 210 220 230 240 QELPQLLDAR SAPLIADQAV LQLLPKTYIL TCEHDVLRDD GIMYAKRLES AGVEVTLDHF 250 260 270 EDGFHGCMIF TSWPTNFSVG IRTRNSYIKW LDQNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Brain, Hippocampus, Testis, Tongue and Trachea.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-343. Tissue: Brain.
[4]	"Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness." Jessani N., Liu Y., Humphrey M., Cravatt B.F. Proc. Natl. Acad. Sci. U.S.A. 99:10335-10340(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, GLYCOSYLATION, SUBCELLULAR LOCATION.
[5]	"An enzyme that regulates ether lipid signaling pathways in cancer annotated by multidimensional profiling." Chiang K.P., Niessen S., Saghatelian A., Cravatt B.F. Chem. Biol. 13:1041-1050(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages." Okazaki H., Igarashi M., Nishi M., Sekiya M., Tajima M., Takase S., Takanashi M., Ohta K., Tamura Y., Okazaki S., Yahagi N., Ohashi K., Amemiya-Kudo M., Nakagawa Y., Nagai R., Kadowaki T., Osuga J., Ishibashi S. J. Biol. Chem. 283:33357-33364(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-287, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB037784 mRNA. Translation: BAA92601.1. Different initiation. AK294811 mRNA. Translation: BAH11890.1. AK295641 mRNA. Translation: BAH12137.1. AK299422 mRNA. Translation: BAH13028.1. Different initiation. AK304253 mRNA. Translation: BAH14142.1. Different initiation. AK316431 mRNA. Translation: BAH14802.1. Different initiation. BC028734 mRNA. Translation: AAH28734.2. Different initiation. BC047588 mRNA. Translation: AAH47588.2. Different initiation.
IPI	IPI00002230. IPI00790972. IPI00924788.
RefSeq	NP_001139748.1. NM_001146276.1. NP_001139749.1. NM_001146277.1. NP_001139750.1. NM_001146278.1. NP_065843.3. NM_020792.4.
UniGene	Hs.444099.
3D structure databases
HSSP	HSSP built from PDB template 2C7B based on UniProtKB Q5G935.
ProteinModelPortal	Q6PIU2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6PIU2. 1 interaction.
STRING	9606.ENSP00000273512.
Protein family/group databases
MEROPS	S09.992.
PTM databases
PhosphoSite	Q6PIU2.
Polymorphism databases
DMDM	74737782.
Proteomic databases
PaxDb	Q6PIU2.
PRIDE	Q6PIU2.
Protocols and materials databases
DNASU	57552.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000475381; ENSP00000418571; ENSG00000144959. ENST00000543711; ENSP00000443227; ENSG00000144959.
GeneID	57552.
KEGG	hsa:57552.
UCSC	uc003fig.3. human.
Organism-specific databases
CTD	57552.
GeneCards	GC03M172348.
H-InvDB	HIX0003864. HIX0163448.
HGNC	HGNC:29260. NCEH1.
HPA	HPA026888.
MIM	613234. gene.
neXtProt	NX_Q6PIU2.
PharmGKB	PA165697847.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0657.
HOVERGEN	HBG058974.
InParanoid	Q6PIU2.
KO	K14349.
OrthoDB	EOG4PVP02.
Gene expression databases
ArrayExpress	Q6PIU2.
Bgee	Q6PIU2.
CleanEx	HS_AADACL1.
Genevestigator	Q6PIU2.
GermOnline	ENSG00000144959. Homo sapiens.
Family and domain databases
InterPro	IPR013094. AB_hydrolase_3. IPR017157. Arylacetamide_deacetylase. IPR002168. Lipase_GDXG_AS. [Graphical view]
Pfam	PF07859. Abhydrolase_3. 2 hits. [Graphical view]
PIRSF	PIRSF037251. Arylacetamide_deacetylase. 1 hit.
PROSITE	PS01173. LIPASE_GDXG_HIS. False negative. PS01174. LIPASE_GDXG_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q6PIU2.
ChEMBL	CHEMBL5048.
ChiTaRS	NCEH1. human.
GenomeRNAi	57552.
NextBio	64018.
SOURCE	Search...

Entry information

Entry name

NCEH1_HUMAN

Accession

Primary (citable) accession number: Q6PIU2
Secondary accession number(s): B7Z2K4 , B7Z3A1, B7Z5U2, B7Z906, B7ZAW6, Q86WZ1, Q9P2I4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	December 12, 2006
Last modified:	May 1, 2013
This is version 81 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.