P53816 (HRSL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HRAS-like suppressor 3
Short name=HRSL3
EC=3.1.1.32
EC=3.1.1.4

Alternative name(s):
Adipose-specific phospholipase A2
Short name=AdPLA
Group XVI phospholipase A1/A2
H-rev 107 protein homolog
HRAS-like suppressor 1
HREV107-1
HREV107-3
Renal carcinoma antigen NY-REN-65

Gene names

Name:	PLA2G16
Synonyms:	HRASLS3, HREV107

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	162 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Exhibits PLA1/2 activity, catalyzing the calcium-independent hydrolysis of acyl groups in various phosphatidylcholines (PC) and phosphatidylethanolamine (PE). For most substrates, PLA1 activity is much higher than PLA2 activity. Specifically catalyzes the release of fatty acids from phospholipids in adipose tissue By similarity. N- and O-acylation activity is hardly detectable. Might decrease protein phosphatase 2A (PP2A) activity. Ref.4 Ref.10
Catalytic activity	Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate. Ref.12 Ref.13 Phosphatidylcholine + H2O = 2-acylglycerophosphocholine + a carboxylate. Ref.12 Ref.13
Subunit structure	Interacts with PPP2R1A; this interaction might decrease PP2A activity. Ref.10
Subcellular location	Cytoplasm. Cytoplasm › perinuclear region By similarity. Membrane; Single-pass membrane protein Ref.10 Ref.12.
Tissue specificity	Widely expressed. low expression, if any, in hematopoietic cells and thymus. In testis, confined to round spermatids. Expressed in normal ovarian epithelial cells. Down-regulated in some ovarian carcinomas and testicular germ cell tumors. Ref.1 Ref.3 Ref.4 Ref.9
Induction	By IFNG and IRF1. Ref.9
Sequence similarities	Belongs to the H-rev107 family.
Biophysicochemical properties	Kinetic parameters: KM=300 µM for dipalmitoyl-PC Ref.4 Vmax=2.57 µmol/min/mg enzyme with dipalmitoyl-PC as substrate Vmax=267 nmol/min/mg enzyme with dipalmitoyl-PE as substrate pH dependence: Optimum pH is 9.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Cytoplasm Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycerophospholipid biosynthetic process Traceable author statement. Source: Reactome lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell cycle Inferred from electronic annotation. Source: Compara phosphatidylcholine acyl-chain remodeling Traceable author statement. Source: Reactome phosphatidylethanolamine acyl-chain remodeling Traceable author statement. Source: Reactome phosphatidylinositol acyl-chain remodeling Traceable author statement. Source: Reactome phosphatidylserine acyl-chain remodeling Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome endoplasmic reticulum Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	1-acyl-2-lysophosphatidylserine acylhydrolase activity Inferred from electronic annotation. Source: EC phosphatidylcholine 1-acylhydrolase activity Inferred from electronic annotation. Source: EC phosphatidylserine 1-acylhydrolase activity Inferred from electronic annotation. Source: EC phospholipase A2 activity Inferred from direct assay PubMed 20100577. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PPP2R1A	P30153	7	EBI-746318,EBI-302388

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 162

162

HRAS-like suppressor 3

PRO_0000152484

Regions

Topological domain

1 – 132

132

Cytoplasmic Potential

Transmembrane

133 – 155

23

Helical; Potential

Topological domain

156 – 162

7

Lumenal Potential

Sites

Active site

23

1

Ref.11 Ref.12 Ref.13

Active site

35

1

Ref.11 Ref.12 Ref.13

Active site

113

1

Acyl-thioester intermediate Ref.11 Ref.12 Ref.13

Experimental info

Mutagenesis

23

1

H → A: No effect on PPP2R1A-binding. Ref.10

Mutagenesis

113

1

C → S: No effect on PPP2R1A-binding. Ref.10

Sequence conflict

90

1

S → T in CAA63423. Ref.1

Sequence conflict

90

1

S → T in BAH08749. Ref.4

Secondary structure

1

.

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.

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162

Helix Strand Turn

Details...

Beta strand

13 – 18

6

Beta strand

21 – 29

9

Beta strand

32 – 37

6

Beta strand

41 – 43

3

Beta strand

45 – 48

4

Helix

49 – 52

4

Beta strand

59 – 64

6

Helix

65 – 69

5

Beta strand

72 – 76

5

Helix

79 – 82

4

Helix

89 – 98

10

Turn

99 – 101

3

Beta strand

103 – 106

4

Helix

110 – 122

13

Sequences

	Sequence		Length	Mass (Da)
	P53816 [UniParc]. Last modified January 31, 2002. Version 2. Checksum: 3565BFC756A6DA3C	FASTA	162	17,937
	10 20 30 40 50 60 MRAPIPEPKP GDLIEIFRPF YRHWAIYVGD GYVVHLAPPS EVAGAGAASV MSALTDKAIV 70 80 90 100 110 120 KKELLYDVAG SDKYQVNNKH DDKYSPLPCS KIIQRAEELV GQEVLYKLTS ENCEHFVNEL 130 140 150 160 RYGVARSDQV RDVIIAASVA GMGLAAMSLI GVMFSRNKRQ KQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12." Husmann K., Sers C., Fietze E., Mincheva A., Lichter P., Schafer R. Oncogene 17:1305-1312(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Human cDNA encoding H-REV107 protein homolog." Kato S. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"hH-Rev107, a class II tumor suppressor gene, is expressed by post-meiotic testicular germ cells and CIS cells but not by human testicular germ cell tumors." Siegrist S., Feral C., Chami M., Solhonne B., Mattei M.G., Rajpert-De Meyts E., Guellaen G., Bulle F. Oncogene 20:5155-5163(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Testis.
[4]	"Characterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes." Uyama T., Jin X.H., Tsuboi K., Tonai T., Ueda N. Biochim. Biophys. Acta 1791:1114-1124(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES. Tissue: Testis.
[5]	"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]. Tissue: Hippocampus.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Colon.
[8]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[9]	"The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNgamma-induced cell death in human ovarian carcinoma cells." Sers C., Husmann K., Nazarenko I., Reich S., Wiechen K., Zhumabayeva B., Adhikari P., Schroder K., Gontarewicz A., Schafer R. Oncogene 21:2829-2839(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[10]	"Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells." Nazarenko I., Schafer R., Sers C. J. Cell Sci. 120:1393-1404(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PPP2R1A, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-23 AND CYS-113.
[11]	"Solution structure of the N-terminal catalytic domain of human H-REV107 -- a novel circular permutated NlpC/P60 domain." Ren X., Lin J., Jin C., Xia B. FEBS Lett. 584:4222-4226(2010) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-125, ACTIVE SITE.
[12]	"Structural basis for the acyltransferase activity of lecithin:retinol acyltransferase-like proteins." Golczak M., Kiser P.D., Sears A.E., Lodowski D.T., Blaner W.S., Palczewski K. J. Biol. Chem. 287:23790-23807(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 1-132, CATALYTIC ACTIVITY, ACTIVE SITE, SUBCELLULAR LOCATION.
[13]	"Structure/Function relationships of adipose phospholipase A2 containing a cys-his-his catalytic triad." Pang X.Y., Cao J., Addington L., Lovell S., Battaile K.P., Zhang N., Rao J.L., Dennis E.A., Moise A.R. J. Biol. Chem. 287:35260-35274(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1-134, CATALYTIC ACTIVITY, ACTIVE SITE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X92814 mRNA. Translation: CAA63423.1.
AB030814 mRNA. Translation: BAB08108.1.
AF317086 mRNA. Translation: AAL26892.1.
AB439591 mRNA. Translation: BAH08749.1.
AK313075 mRNA. Translation: BAG35901.1.
CH471076 Genomic DNA. Translation: EAW74158.1.
BC001387 mRNA. Translation: AAH01387.1.
BC103807 mRNA. Translation: AAI03808.1.

IPI

IPI00296480.

RefSeq

NP_001121675.1. NM_001128203.1.
NP_009000.2. NM_007069.3.

UniGene

Hs.502775.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KYT	NMR	-	A	1-125	[»]
4DOT	X-ray	1.96	A	1-132	[»]
4FA0	X-ray	2.65	A	1-134	[»]

ProteinModelPortal

P53816.

ModBase

Search...

Protein-protein interaction databases

IntAct

P53816. 3 interactions.

MINT

MINT-1461468.

STRING

9606.ENSP00000320337.

PTM databases

PhosphoSite

P53816.

Polymorphism databases

DMDM

20141767.

Proteomic databases

PaxDb

P53816.

PRIDE

P53816.

Protocols and materials databases

DNASU

11145.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000323646; ENSP00000320337; ENSG00000176485.
ENST00000415826; ENSP00000389124; ENSG00000176485.

GeneID

11145.

KEGG

hsa:11145.

UCSC

uc001nxh.2. human.

Organism-specific databases

CTD

11145.

GeneCards

GC11M063341.

HGNC

HGNC:17825. PLA2G16.

MIM

613867. gene.

neXtProt

NX_P53816.

PharmGKB

PA164724584.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG69032.

HOGENOM

HOG000293227.

InParanoid

P53816.

KO

K16817.

OMA

QVRDAIM.

OrthoDB

EOG4WSWBT.

PhylomeDB

P53816.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P53816.

Bgee

P53816.

CleanEx

HS_PLA2G16.

Genevestigator

P53816.

GermOnline

ENSG00000176485. Homo sapiens.

Family and domain databases

InterPro

IPR007053. LRAT-like_dom.
[Graphical view]

Pfam

PF04970. LRAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

11145.

NextBio

42368.

SOURCE

Search...

Entry information

Entry name

HRSL3_HUMAN

Accession

Primary (citable) accession number: P53816
Secondary accession number(s): B2R7Q4 , B7XAK5, Q3SYI3, Q9HDD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 31, 2002
Last modified:	May 29, 2013
This is version 109 of the entry and version 2 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.