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SPPL2A Gene

protein-coding GIFtS: 55
GCID: GC15M050999

Signal Peptide Peptidase Like 2A

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disease database

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
Signal Peptide Peptidase Like 2A¹ ²		SPP-Like 2A² ³
Intramembrane Protease 3¹ ² ³		Intramembrane Cleaving Protease²
Presenilin-Like Protein 2¹ ² ³		Signal Peptide Peptidase-Like 2A²
IMP3² ³ ⁵		EC 3.4.23.-³
IMP-3² ³		SPPL2a³
PSL2² ³

External Ids:	HGNC: 30227¹	Entrez Gene: 84888²	Ensembl: ENSG00000138600⁷	OMIM: 608238⁵	UniProtKB: Q8TCT8³

Export aliases for SPPL2A gene to outside databases

Previous GC identifers: GC15M046557 GC15M044045 GC15M048578 GC15M048715 GC15M048787 GC15M027830

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SPPL2A Gene:

This gene encodes a member of the GXGD family of aspartic proteases, which are transmembrane proteins with two

conserved catalytic motifs localized within the membrane-spanning regions, as well as a member of the signal

peptide peptidase-like protease (SPPL) family. This protein is expressed in all major adult human tissues and

localizes to late endosomal compartments and lysosomal membranes. A pseudogene of this gene also lies on

chromosome 15. (provided by RefSeq, Feb 2012)

GeneCards Summary for SPPL2A Gene:

SPPL2A (signal peptide peptidase like 2A) is a protein-coding gene. GO annotations related to this gene include aspartic-type endopeptidase activity and protein homodimerization activity. An important paralog of this gene is HM13.

UniProtKB/Swiss-Prot: SPP2A_HUMAN, Q8TCT8

Function: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the

hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing. Catalyzes the intramembrane

cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain

(ICD) for signaling to the nucleus. Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG,

which promotes the release of the intracellular FasL domain (FasL ICD). May play a role in the regulation of

innate and adaptive immunity

Gene Wiki entry for SPPL2A Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence at NCBI GenBank:

NC_000015.9 NT_010194.18 NC_018926.2

Regulatory elements:

Regulatory transcription factor binding sites in the SPPL2A gene promoter:
GR Elk-1 E47 Evi-1 MEF-2A POU2F1 POU2F1a GR-alpha aMEF-2 RSRFC4
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: SPPL2A promoter sequence

Search Chromatin IP Primers for SPPL2A

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SPPL2A

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 15q21.2 Ensembl cytogenetic band: 15q21.2 HGNC cytogenetic band: 15q21.2

SPPL2A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SPPL2A gene location

GeneLoc information about chromosome 15 GeneLoc Exon Structure

GeneLoc location for GC15M050999: view genomic region (about GC identifiers)

Start:	50,999,506 bp from pter	End:	51,058,005 bp from pter
Size:	58,500 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, antibodies-online, and/or GeneTex,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
About This Section

UniProtKB/Swiss-Prot: SPP2A_HUMAN, Q8TCT8 (See protein sequence)

Recommended Name: Signal peptide peptidase-like 2A precursor

Size: 520 amino acids; 58143 Da

Subunit: Interacts with ITM2B

Sequence caution: Sequence=BAB55117.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

Sequence=CAD13133.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

Secondary accessions: B2RDS0 Q8TAW1 Q96SZ8

Explore the universe of human proteins at neXtProt for SPPL2A: NX_Q8TCT8

Explore proteomics data for SPPL2A at MOPED

Post-translational modifications:

Glycosylated¹

Glycosylation² at Asn58, Asn66, Asn74, Asn116, Asn126, Asn149, Asn155

Modification sites at PhosphoSitePlus

See SPPL2A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_116191.2

ENSEMBL proteins:

ENSP00000261854 ENSP00000453927 ENSP00000453932

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	antibodies-online peptides for SPPL2A

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GenesLikeMe)
About This Section

3 InterPro protein domains:

IPR006639 Preselin/SPP

IPR003137 Protease-assoc_domain

IPR007369 Peptidase_A22B_SPP

Graphical View of Domain Structure for InterPro Entry Q8TCT8

ProtoNet protein and cluster: Q8TCT8

1 Blocks protein domain: IPB003137 Protease-associated PA

UniProtKB/Swiss-Prot: SPP2A_HUMAN, Q8TCT8

Domain: The PAL motif is required for normal active site conformation (By similarity). The catalytic domains

embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it

is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP

Similarity: Belongs to the peptidase A22B family

Similarity: Contains 1 PA (protease associated) domain

Find genes that share domains with SPPL2A About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: SPP2A_HUMAN, Q8TCT8

Function: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the

hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing. Catalyzes the intramembrane

cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain

(ICD) for signaling to the nucleus. Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG,

which promotes the release of the intracellular FasL domain (FasL ICD). May play a role in the regulation of

innate and adaptive immunity

Enzyme Number (IUBMB): EC 3.4.23.-¹

Gene Ontology (GO): 3 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004190	aspartic-type endopeptidase activity	IEA	--
GO:0005515	protein binding	IPI	17965014
GO:0042803	protein homodimerization activity	IDA	15385547

Find genes that share ontologies with SPPL2A About GenesLikeMe

Phenotypes:
2 GenomeRNAi human phenotypes for SPPL2A:

Increased G1 DNA content

Increased HPV18 LCR reporter a

3 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Sppl2a):

cellular

hematopoietic system

immune system

Find genes that share phenotypes with SPPL2A About GenesLikeMe

Animal Models:
MGI mouse knock-outs for SPPL2A: Sppl2a^tm1Basc Sppl2a^tm1Dgen

genOway: Develop your customized and physiologically relevant rodent model for SPPL2A

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In Situ Assay
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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Subcellular locations from UniProtKB/Swiss-Prot

SPP2A_HUMAN, Q8TCT8: Late endosome membrane; Multi-pass membrane protein (By similarity). Lysosome membrane;

Multi-pass membrane protein (By similarity). Cell membrane. Note=Colocalizes with palmitoylated and myristoylated

proteins at the plasma membrane

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
endoplasmic reticulum	5
endosome	5
golgi apparatus	5
lysosome	5
plasma membrane	5
vacuole	5
cytosol	1

About this image

Gene Ontology (GO): Selected cellular component terms (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005765	lysosomal membrane	IDA	17897319
GO:0005886	plasma membrane	IEA	--
GO:0016021	integral component of membrane	--	--
GO:0030660	Golgi-associated vesicle membrane	IDA	17965014
GO:0031902	late endosome membrane	IEA	--

Find genes that share ontologies with SPPL2A About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GenesLikeMe, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for SPPL2A
Interactions:

Search GeneGlobe Interaction Network for SPPL2A

STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

5 Interacting proteins for SPPL2A (Q8TCT8^{2, 3} ENSP00000261854⁴) via UniProtKB, MINT, STRING, and/or I2D

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
SGTA	O43765²^,³, ENSP00000221566⁴	MINT-67903 I2D: score=5 STRING: ENSP00000221566
LAMP2	P13473³, ENSP00000408411⁴	I2D: score=1 STRING: ENSP00000408411
TFRC	P02786²	MINT-8412736
SUGT1	ENSP00000367208⁴	STRING: ENSP00000367208
NFKB1	ENSP00000226574⁴	STRING: ENSP00000226574

About this table

Gene Ontology (GO): 3 biological process terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006509	membrane protein ectodomain proteolysis	IDA	16829951
GO:0031293	membrane protein intracellular domain proteolysis	IMP	16829952
GO:0050776	regulation of immune response	IMP	16829952

Find genes that share ontologies with SPPL2A About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, Sets of similar genes according to GenesLikeMe)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for SPPL2A (SPP2A)

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
About This Section

REFSEQ mRNAs for SPPL2A gene (4 alternative transcripts):

NM_032802.3 XM_005254722.1 XM_005254723.1 XM_005254724.1

Unigene Cluster for SPPL2A:

Signal peptide peptidase like 2A

Hs.401537 [show with all ESTs]

Unigene Representative Sequence: BC025740

7 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000261854(uc001zyv.3) ENST00000558934 ENST00000559293 ENST00000558146

ENST00000559527 ENST00000558414 ENST00000560288

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Additional mRNA sequence:

AJ345028.1 AJ420896.1 AK027446.1 AK075454.1 AK315651.1 AY169314.1 BC025740.1

11 DOTS entries:

DT.113009 DT.100784170 DT.100784166 DT.95374734 DT.65285814 DT.100784167 DT.91742488 DT.91742490

DT.97841869 DT.99947206 DT.95374728

Selected AceView cDNA sequences (see all 73):

BC025740 BI770056 BP338432 BI492849 NM_032802 AW304186 AA988423 CR626792

AJ420896 BU633276 AY169314 BQ016314 BP343058 AJ345028 BQ049401 BE465131

BU076239 BI764078 BU676225 AK027446 BI834817 AI823363 BG541552 CA841385

GeneLoc Exon Structure

4 Alternative Splicing Database (ASD) splice patterns (SP) for SPPL2A About this scheme

ExUns:	1	^	2	^	3	^	4a	·	4b	^	5	^	6	^	7	^	8	^	9	^	10	^	11	^	12	^	13a	·	13b	·	13c	^	14	^	15a	·	15b	^	16	^	17
SP1:									-														-		-						-
SP2:
SP3:
SP4:

ECgene alternative splicing isoforms for SPPL2A

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GenesLikeMe, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

SPPL2A expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: ATACTTACAT

About this image

SPPL2A Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

SPPL2A Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.401537

UniProtKB/Swiss-Prot: SPP2A_HUMAN, Q8TCT8

Tissue specificity: Ubiquitous

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for SPPL2A gene from Selected species (see all 14) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Sppl2a^{1 , 5}	RIKEN cDNA 2010106G01 gene⁵ signal peptide peptidase like 2A¹	83.75(n)¹ 80.54(a)¹		2 (61.76 cM)⁵ 66552¹ NM_023220.2¹ NP_075709.2¹ 126890391⁵
chicken (Gallus gallus)	Aves	SPPL2A¹	signal peptide peptidase like 2A	74.37(n) 71.78(a)		415450 NM_001012769.1 NP_001012787.1
lizard (Anolis carolinensis)	Reptilia	SPPL2A⁶	signal peptide peptidase like 2A	53(a)	1 ↔ 1	GL343747.1(82531-196635)
tropical clawed frog (Xenopus tropicalis)	Amphibia	sppl2a¹	signal peptide peptidase like 2A	65.36(n) 61.89(a)		100135083 NM_001113822.1 NP_001107294.1
zebrafish (Danio rerio)	Actinopterygii	zgc:123258¹	zgc:123258	55.67(n) 51.06(a)		641502 NM_001037439.1 NP_001032516.1
worm (Caenorhabditis elegans)	Secernentea	C36B1.12³ imp-1¹	imp-1¹	28(a)³ 48.54(n)¹ 33.63(a)¹		I(8760309-8763421)³ 172684¹ NM_001025854.3¹ NP_001021025.1¹
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	--	Putative protein of unknown function with similari...	16(a)	1 → many	XI(253697-255460) YKL100C
rice (Oryza sativa)	Liliopsida	Os11g0433200¹	Os11g0433200	48.02(n) 35.12(a)		4350402 NM_001074329.1 NP_001067797.1

ENSEMBL Gene Tree for SPPL2A (if available)
TreeFam Gene Tree for SPPL2A (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68,Sets of similar genes according to GenesLikeMe)
About This Section

Paralogs for SPPL2A gene

HM13² SPPL2C² SPPL3²

2 SIMAP similar genes for SPPL2A using alignment to 3 protein entries: SPP2A_HUMAN (see all proteins):

SPPL2B SPPL2C

Find genes that share paralogs with SPPL2A About GenesLikeMe

1 Pseudogenes.org Pseudogene for SPPL2A
PGOHUM00000246782

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
About This Section

SNP ID	Valid	Clinical significance	Chr 15 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs72740493^1,2	C,F	--	50999258(+)	`TCACCG/TTTGAA`	1	--	ds500¹		3		WA NA EA	358
rs12911654^1,2	C,F,A,H	--	50999299(+)	`TTCTAC/TAGAGC`	1	--	ds500¹		12		NS EA NA CSA WA	776
rs12912841^1,2		--	50999332(+)	`TTTTTT/GTGGGA`	1	--	ds500¹		2		NA	122
rs12912843^1,2	C	--	50999333(+)	`TTTTTG/TGGGAT`	1	--	ds500¹		1		NA	2
rs78789557^1,2	C	--	50999391(+)	`GCTCAC/GTGCAA`	1	--	ds500¹		0	--	--	--	--
rs28373855^1,2		--	50999488(+)	`TTTTTG/TGTATT`	1	--	ds500¹		0	--	--	--	--
rs150435817^1,2	C	--	50999516(+)	`TCACCA/GTGTTA`	1	--	ds500¹		0	--	--	--	--
rs183865904^1,2		--	50999536(+)	`GTCTCA/GATCTC`	1	--	ds500¹		0	--	--	--	--
rs188643878^1,2	C	--	50999561(+)	`CGCCCA/GCCTTG`	1	--	ds500¹		0	--	--	--	--
rs138117429^1,2		--	50999582(+)	`GTGTTC/GGGATT`	1	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for SPPL2A (50999506 - 51058005 bp)

Structural Variations
Database of Genomic Variants (DGV) 7 variations for SPPL2A: About this table

Variant ID	Type	Subtype	PubMed ID
esv2609237	CNV	Deletion	19546169
esv2659888	CNV	Deletion	23128226
nsv457137	CNV	Loss	19166990
nsv904213	CNV	Loss	21882294
nsv904212	CNV	Gain	21882294
dgv317n27	CNV	Gain	19166990
nsv471242	CNV	Gain	18288195

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB, Sets of similar genes according to GenesLikeMe)
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OMIM gene information: 608238 OMIM disorders: --

Find genes that share disorders with SPPL2A About GenesLikeMe

1 Novoseek inferred disease relationship for SPPL2A gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
alzheimers disease	48.8	1	15549135 (1)

Export disorders for SPPL2A gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for SPPL2A gene, integrated from 10 sources (see all 44):
(articles sorted by number of sources associating them with SPPL2A)

Novel class of polytopic proteins with domains associated with putative protease activity. (PubMed id 12139484)^{1, 2, 3} Grigorenko A.P.... Rogaev E.I. (Biokhimiia 2002)
Identification of signal peptide peptidase, a presenilin-type aspartic protease. (PubMed id 12077416)^{1, 2, 3} Weihofen A.... Martoglio B. (Science 2002)
Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins. (PubMed id 15385547)^{1, 2, 9} Friedmann E.... Martoglio B. (J. Biol. Chem. 2004)
Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. (PubMed id 17965014)^{1, 2, 9} Martin L.... Haass C. (J. Biol. Chem. 2008)
The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. (PubMed id 17557115)^{1, 2, 9} Kirkin V....Zornig M. (Cell Death Differ. 2007)
A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b. (PubMed id 16829951)^{1, 2} Fluhrer R....Haass C. (Nat. Cell Biol. 2006)
SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. (PubMed id 16829952)^{1, 2} Friedmann E.... Martoglio B. (Nat. Cell Biol. 2006)
Signal sequence and keyword trap in silico for selection of full- length human cDNAs encoding secretion or membrane proteins from oligo- capped cDNA libraries. (PubMed id 16303743)^{1, 2} Otsuki T....Isogai T. (DNA Res. 2005)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (Nat. Genet. 2004)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S.... Malek J. (Genome Res. 2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 84888	HGNC: 30227	AceView: SPPL2A	Ensembl:ENSG00000138600	euGenes: HUgn84888
ECgene: SPPL2A	H-InvDB: SPPL2A

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for SPPL2A	Pharmacogenomics, SNPs, Pathways

Intellectual Property for SPPL2A gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for SPPL2A gene:
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GeneCards and IP:
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Signal Peptide Peptidase Like 2A

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