PLA2G6 phospholipase A2 group VI [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLA2G6provided by HGNC
Official Full Name: phospholipase A2 group VIprovided by HGNC
Primary source: HGNC:HGNC:9039
See related: Ensembl:ENSG00000184381 MIM:603604; AllianceGenome:HGNC:9039
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GVI; PLA2; INAD1; NBIA2; iPLA2; NBIA2A; NBIA2B; PARK14; PNPLA9; CaI-PLA2; IPLA2-VIA; iPLA2beta
Summary: The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]
Expression: Broad expression in testis (RPKM 12.7), gall bladder (RPKM 8.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q13.1

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (38111495..38181830, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (38574672..38644982, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (38507502..38577837, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

An estimation of global genetic prevalence of PLA2G6-associated neurodegeneration.
Title: An estimation of global genetic prevalence of PLA2G6-associated neurodegeneration.
Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing.
Title: Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing.
The role of the PLA2G6 gene in neurodegenerative diseases.
Title: The role of the PLA2G6 gene in neurodegenerative diseases.
Phenotype and genotype heterogeneity of PLA2G6-associated neurodegeneration in a cohort of pediatric and adult patients.
Title: Phenotype and genotype heterogeneity of PLA2G6-associated neurodegeneration in a cohort of pediatric and adult patients.
PLA2G6-associated late-onset parkinsonism in a Sudanese family.
Title: PLA2G6-associated late-onset parkinsonism in a Sudanese family.
Association between PLA2 gene polymorphisms and treatment response to antipsychotic medications: A study of antipsychotic-naive first-episode psychosis patients and nonadherent chronic psychosis patients.
Title: Association between PLA2 gene polymorphisms and treatment response to antipsychotic medications: A study of antipsychotic-naïve first-episode psychosis patients and nonadherent chronic psychosis patients.
Molecular basis of unique specificity and regulation of group VIA calcium-independent phospholipase A2 (PNPLA9) and its role in neurodegenerative diseases.
Title: Molecular basis of unique specificity and regulation of group VIA calcium-independent phospholipase A(2) (PNPLA9) and its role in neurodegenerative diseases.
Whole genome sequencing reveals biallelic PLA2G6 mutations in siblings with cerebellar atrophy and cap myopathy.
Title: Whole genome sequencing reveals biallelic PLA2G6 mutations in siblings with cerebellar atrophy and cap myopathy.
Genome sequencing reveals novel noncoding variants in PLA2G6 and LMNB1 causing progressive neurologic disease.
Title: Genome sequencing reveals novel noncoding variants in PLA2G6 and LMNB1 causing progressive neurologic disease.
Novel insertion mutation in the PLA2G6 gene in an Iranian family with infantile neuroaxonal dystrophy.
Title: Novel insertion mutation in the PLA2G6 gene in an Iranian family with infantile neuroaxonal dystrophy.

Submit: New GeneRIF Correction See all GeneRIFs (135)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal recessive Parkinson disease 14 MedGen: C2751842 OMIM: 612953 GeneReviews: Parkinson Disease Overview	not available
Infantile neuroaxonal dystrophy MedGen: C0270724 OMIM: 256600 GeneReviews: PLA2G6-Associated Neurodegeneration, Neurodegeneration with Brain Iron Accumulation Disorders Overview	not available
Neurodegeneration with brain iron accumulation 2B MedGen: C1857747 OMIM: 610217 GeneReviews: PLA2G6-Associated Neurodegeneration	not available

EBI GWAS Catalog

Description
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies three loci associated with melanoma risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies three new melanoma susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor	PubMed
	env	HIV-1 gp120 induces a specific phospholipase A2 (PLA2) activation in lymphocytes through binding to CD4, but this effect is not sufficient to accomplish virus/cell fusion	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PLA2G6_1043 (e-PCR)
- UniSTS:277587

G49410 (e-PCR)
- UniSTS:109155

L17877 (e-PCR)
- UniSTS:61334

RH99077 (e-PCR)
- UniSTS:92823

L17809 (e-PCR)
- UniSTS:39087

G49249 (e-PCR)
- UniSTS:109005

G49250 (e-PCR)
- UniSTS:109006

G49251 (e-PCR)
- UniSTS:109007

G49252 (e-PCR)
- UniSTS:109008

G49253 (e-PCR)
- UniSTS:109009

G49254 (e-PCR)
- UniSTS:109010

G49255 (e-PCR)
- UniSTS:109011

G49256 (e-PCR)
- UniSTS:109012

G49257 (e-PCR)
- UniSTS:109013

G49258 (e-PCR)
- UniSTS:109014

G49259 (e-PCR)
- UniSTS:109015

D22S622 (e-PCR)
- UniSTS:149723

GDB:631802 (e-PCR)
- UniSTS:158429

AL022554 (e-PCR)
- UniSTS:15097

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 1-alkyl-2-acetylglycerophosphocholine esterase activity	ISS Inferred from Sequence or Structural Similarity more info
enables calcium-independent phospholipase A2 activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-independent phospholipase A2 activity	IDA Inferred from Direct Assay more info	PubMed
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables hydrolase activity	TAS Traceable Author Statement more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables long-chain fatty acyl-CoA hydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables long-chain fatty acyl-CoA hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
enables lysophospholipase activity	IDA Inferred from Direct Assay more info	PubMed
enables phospholipase A2 activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine hydrolase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Fc-gamma receptor signaling pathway involved in phagocytosis	TAS Traceable Author Statement more info
involved_in antibacterial humoral response	IDA Inferred from Direct Assay more info	PubMed
involved_in cardiolipin acyl-chain remodeling	IBA Inferred from Biological aspect of Ancestor more info
involved_in cardiolipin acyl-chain remodeling	IDA Inferred from Direct Assay more info	PubMed
involved_in cardiolipin acyl-chain remodeling	TAS Traceable Author Statement more info	PubMed
involved_in cardiolipin biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in phosphatidic acid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in phosphatidylcholine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylethanolamine catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in platelet activating factor metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of ceramide biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in microtubule cytoskeleton	IDA Inferred from Direct Assay more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
is_active_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear speck	IDA Inferred from Direct Assay more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in pseudopodium	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: 85/88 kDa calcium-independent phospholipase A2

Names: 2-lysophosphatidylcholine acylhydrolase; 85 kDa calcium-independent phospholipase A2; GVI PLA2; iPLA2-beta; intracellular membrane-associated calcium-independent phospholipase A2 beta; neurodegeneration with brain iron accumulation 2; palmitoyl-CoA hydrolase; patatin-like phospholipase domain-containing protein 9; phospholipase A2, group VI (cytosolic, calcium-independent)

NP_001004426.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_001186491.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_001336793.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_001336794.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_001336795.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_001336796.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_001336797.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_001336798.1

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NP_003551.2

EC 3.1.1.4

EC 3.1.1.5

EC 3.1.2.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007094.3 RefSeqGene

Range

37949..108284

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1015

mRNA and Protein(s)

NM_001004426.3 → NP_001004426.1 85/88 kDa calcium-independent phospholipase A2 isoform b

See identical proteins and their annotated locations for NP_001004426.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but lacks an internal segment compared to isoform a. Variants 2, 3, 5 and 6 encode the same isoform (b). Isoform b is found in the cytoplasm while isoform a is membrane-bound.

Source sequence(s)

AF064594, BC036742, BC051904, DC376896

Consensus CDS

CCDS33645.1

UniProtKB/TrEMBL

A8K460

Related

ENSP00000335149.3, ENST00000335539.7

Conserved Domains (4) summary

cd07212
Location:426 → 739

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:214 → 370

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:286 → 314

ANK; ANK repeat [structural motif]

pfam13637
Location:350 → 395

Ank_4; Ankyrin repeats (many copies)
NM_001199562.3 → NP_001186491.1 85/88 kDa calcium-independent phospholipase A2 isoform b

See identical proteins and their annotated locations for NP_001186491.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and lacks an in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but lacks an internal segment compared to isoform a. Variants 2, 3, 5 and 6 encode the same protein (isoform b). Isoform b is found in the cytoplasm while isoform a is membrane-bound.

Source sequence(s)

AF064594, AK290825, BC051904, DC409316

Consensus CDS

CCDS33645.1

UniProtKB/TrEMBL

A8K460

Related

ENSP00000386100.1, ENST00000402064.5

Conserved Domains (4) summary

cd07212
Location:426 → 739

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:214 → 370

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:286 → 314

ANK; ANK repeat [structural motif]

pfam13637
Location:350 → 395

Ank_4; Ankyrin repeats (many copies)
NM_001349864.2 → NP_001336793.1 85/88 kDa calcium-independent phospholipase A2 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1. Both variants 1 and 4 encode the same protein (isoform a). Isoform a is membrane-bound while isoform b is found in the cytoplasm.

Source sequence(s)

AF064594, BC036742, BC051904, DC376896

Consensus CDS

CCDS13967.1

UniProtKB/Swiss-Prot

A8K597, B0QYE8, O60733, O75645, Q8N452, Q9UG29, Q9UIT0, Q9Y671

UniProtKB/TrEMBL

A0A590UJC7

Related

ENSP00000499712.1, ENST00000663895.1

Conserved Domains (3) summary

cd07212
Location:480 → 793

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:285 → 403

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:286 → 314

ANK; ANK repeat [structural motif]
NM_001349865.2 → NP_001336794.1 85/88 kDa calcium-independent phospholipase A2 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and lacks an in-frame exon in the central coding region, compared to variant 1. The resulting isoform (b) has the same N- and C-termini but lacks an internal segment compared to isoform a. Variants 2, 3, 5 and 6 encode the same isoform (b). Isoform b is found in the cytoplasm while isoform a is membrane-bound.

Source sequence(s)

AF064594, AK290825, BC051904, DC318003, DC376896

Consensus CDS

CCDS33645.1

UniProtKB/TrEMBL

A8K460

Conserved Domains (4) summary

cd07212
Location:426 → 739

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:214 → 370

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:286 → 314

ANK; ANK repeat [structural motif]

pfam13637
Location:350 → 395

Ank_4; Ankyrin repeats (many copies)
NM_001349866.2 → NP_001336795.1 85/88 kDa calcium-independent phospholipase A2 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and lacks an in-frame exon in the central coding region, compared to variant 1. The resulting isoform (b) has the same N- and C-termini but lacks an internal segment compared to isoform a. Variants 2, 3, 5 and 6 encode the same isoform (b). Isoform b is found in the cytoplasm while isoform a is membrane-bound.

Source sequence(s)

AF064594, BC051904, DC400693

Consensus CDS

CCDS33645.1

UniProtKB/TrEMBL

A8K460

Conserved Domains (4) summary

cd07212
Location:426 → 739

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:214 → 370

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:286 → 314

ANK; ANK repeat [structural motif]

pfam13637
Location:350 → 395

Ank_4; Ankyrin repeats (many copies)
NM_001349867.2 → NP_001336796.1 85/88 kDa calcium-independent phospholipase A2 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (7) contains multiple differences in the 5' UTR, one of which results in use of a downstream start codon, compared to variant 1. The resulting isoform (c) has a shorter N-terminus than isoform a.

Source sequence(s)

AF064594, AK290825, BC051904, DA290853, DA500195, DC409316

UniProtKB/TrEMBL

B3KU52

Conserved Domains (4) summary

cd07212
Location:302 → 615

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:107 → 225

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:108 → 136

ANK; ANK repeat [structural motif]

cl26073
Location:12 → 199

Ank_2; Ankyrin repeats (3 copies)
NM_001349868.2 → NP_001336797.1 85/88 kDa calcium-independent phospholipase A2 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (8) differs in the 5' UTR and lacks an exon in the 5' coding region, compared to variant 1. These differences result in use of an alternate start codon, resulting in an isoform (d) with a shorter and distinct N-terminus compared to isoform a.

Source sequence(s)

AF064594, BC036742, BC051904, BE278797, DC409316

UniProtKB/TrEMBL

B3KU52

Conserved Domains (3) summary

cd07212
Location:254 → 567

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:59 → 177

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:60 → 88

ANK; ANK repeat [structural motif]
NM_001349869.2 → NP_001336798.1 85/88 kDa calcium-independent phospholipase A2 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (9) contains multiple differences in the 5' UTR, one of which results in use of a downstream start codon, and lacks an alternate in-frame exon in the central coding region, compared to variant 1. The resulting isoform (e) has a shorter N-terminus and lacks an internal segment compared to isoform a.

Source sequence(s)

AF064594, AK290825, BC051904, BP251849, DA290853, DC409316

Conserved Domains (4) summary

cd07212
Location:248 → 561

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:36 → 192

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:108 → 136

ANK; ANK repeat [structural motif]

pfam13637
Location:172 → 217

Ank_4; Ankyrin repeats (many copies)
NM_003560.4 → NP_003551.2 85/88 kDa calcium-independent phospholipase A2 isoform a

See identical proteins and their annotated locations for NP_003551.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a). Both variants 1 and 4 encode the same protein (isoform a). Isoform a is membrane-bound while isoform b is found in the cytoplasm.

Source sequence(s)

AF064594, BC036742, BC051904, DC376896

Consensus CDS

CCDS13967.1

UniProtKB/Swiss-Prot

A8K597, B0QYE8, O60733, O75645, Q8N452, Q9UG29, Q9UIT0, Q9Y671

UniProtKB/TrEMBL

A0A590UJC7

Related

ENSP00000333142.3, ENST00000332509.8

Conserved Domains (3) summary

cd07212
Location:480 → 793

Pat_PNPLA9; Patatin-like phospholipase domain containing protein 9

cd00204
Location:285 → 403

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:286 → 314

ANK; ANK repeat [structural motif]