SPPL2C (signal peptide peptidase like 2C)

Gene

• Entrez ID: 162540
• Gene name: Signal peptide peptidase like 2C
• Gene symbol: SPPL2C
• Synonyms (NCBI Gene): IMP5
• Chromosome: 17
• Chromosome location: 17q21.31

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017486	hsa-miR-335-5p	Microarray	18185580

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001675	Process	Acrosome assembly	IEA
GO:0001675	Process	Acrosome assembly	ISS
GO:0004190	Function	Aspartic-type endopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005765	Component	Lysosomal membrane	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	16829952
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0006508	Process	Proteolysis	IEA
GO:0006509	Process	Membrane protein ectodomain proteolysis	IMP	17965014
GO:0006874	Process	Intracellular calcium ion homeostasis	IEA
GO:0006874	Process	Intracellular calcium ion homeostasis	ISS
GO:0007283	Process	Spermatogenesis	IEA
GO:0007342	Process	Fusion of sperm to egg plasma membrane involved in single fertilization	IEA
GO:0007342	Process	Fusion of sperm to egg plasma membrane involved in single fertilization	ISS
GO:0008233	Function	Peptidase activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030660	Component	Golgi-associated vesicle membrane	IBA
GO:0031293	Process	Membrane protein intracellular domain proteolysis	IMP	16829952
GO:0033619	Process	Membrane protein proteolysis	IBA
GO:0035036	Process	Sperm-egg recognition	ISS
GO:0042500	Function	Aspartic endopeptidase activity, intramembrane cleaving	IBA
GO:0042500	Function	Aspartic endopeptidase activity, intramembrane cleaving	IEA
GO:0042500	Function	Aspartic endopeptidase activity, intramembrane cleaving	ISS
GO:0042803	Function	Protein homodimerization activity	IDA	15385547
GO:0042803	Function	Protein homodimerization activity	IEA
GO:0050821	Process	Protein stabilization	IEA
GO:0060090	Function	Molecular adaptor activity	IEA
GO:0098553	Component	Lumenal side of endoplasmic reticulum membrane	IBA
GO:0098553	Component	Lumenal side of endoplasmic reticulum membrane	IDA	15385547
GO:0098553	Component	Lumenal side of endoplasmic reticulum membrane	IEA
GO:0098554	Component	Cytoplasmic side of endoplasmic reticulum membrane	IBA
GO:0098554	Component	Cytoplasmic side of endoplasmic reticulum membrane	IDA	15385547
GO:0098554	Component	Cytoplasmic side of endoplasmic reticulum membrane	IEA

Other IDs

• MIM: 608284
• HGNC: 28902
• e!Ensembl: ENSG00000185294

Protein

• UniProt ID: Q8IUH8
• Protein name: Signal peptide peptidase-like 2C (SPP-like 2C) (SPPL2c) (EC 3.4.23.-) (Intramembrane protease 5) (IMP-5)
• Protein function: Sperm-specific intramembrane-cleaving aspartic protease (I-CLiP) that cleaves distinct tail-anchored proteins and SNARE proteins (PubMed:30733281). In elongated spermatids, modulates intracellular Ca(2+) homeostasis by controlling PLN abundance
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04258	Peptidase_A22B	241 → 532	Signal peptide peptidase	Family

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in testis where it is primarily localised in spermatids (at protein level). {ECO:0000269|PubMed:30733281}.
• Sequence:

  MACLGFLLPVGFLLLISTVAGGKYGVAHVVSENWSKDYCILFSSDYITLPRDLHHAPLLP
  LYDGTKAPWCPGEDSPHQAQLRSPSQRPLRQTTAMVMRGNCSFHTKGWLAQGQGAHGLLI
  VSRVSDQQCSDTTLAPQDPRQPLADLTIPVAMLHYADMLDILSHTRGEAVVRVAMYAPPE
  PIIDYNMLVIFILAVGTVAAGGYWAGLTEANRLQRRRARRGGGSGGHHQLQEAAAAEGAQ
  KEDNEDIPVDFTPAMTGVVVTLSCSLMLLLYFFYDHFVYVTIGIFGLGAGIGLYSCLSPL
  VCRLSLRQYQRPPHSLWASLPLPLLLLASLCATVIIFWVAYRNEDRWAWLLQDTLGISYC
  LFVLHRVRLPTLKNCSSFLLALLAFDVFFVFVTPFFTKTGESIMAQVALGPAESSSHERL
  PMVLKVPRLRVSALTLCSQPFSILGFGDIVVPGFLVAYCCRFDVQVCSRQIYFVACTVAY
  AVGLLVTFMAMVLMQMGQPALLYLVSSTLLTSLAVAACRQELSLFWTGQGRAKMCGLGCA
  PSAGSRQKQEGAADAHTASTLERGTSRGAGDLDSNPGEDTTEIVTISENEATNPEDRSDS
  SEGWSDAHLDPNELPFIPPGASEELMPLMPMAMLIPLMPLMPPPSELGHVHAQAQAHETG
  LPWAGLHKRKGLKVRKSMSTQAPL

• Sequence length: 684

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORTICOBASAL DEGENERATION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alopecia	Alopecia	GWASCAT_DG	28196072		★☆☆☆☆ Found in Text Mining only
Alopecia, Androgenetic, 1	Androgenetic Alopecia	GWASCAT_DG	22693459		★☆☆☆☆ Found in Text Mining only
Alopecia, Androgenetic, 2	Androgenetic Alopecia	GWASCAT_DG	22693459		★☆☆☆☆ Found in Text Mining only
Alopecia, Androgenetic, 3	Androgenetic Alopecia	GWASCAT_DG	22693459		★☆☆☆☆ Found in Text Mining only
Alopecia, Male Pattern	Alopecia, Male Pattern	GWASCAT_DG	22693459		★☆☆☆☆ Found in Text Mining only
Alopecia, Male Pattern	Alopecia, Male Pattern	GWASDB_DG	22693459		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	33637690	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Androgenetic Alopecia	Androgenetic Alopecia	GWASCAT_DG	22693459		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	37761960	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	GWASCAT_DG	30804561		★☆☆☆☆ Found in Text Mining only
Corticobasal degeneration	Corticobasal Degeneration	GWASCAT_DG	26077951		★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Pulmonary Fibrosis	BEFREE	24429156		★☆☆☆☆ Found in Text Mining only
Lung Diseases Interstitial	Lung disease	Pubtator	26792595	Associate	★☆☆☆☆ Found in Text Mining only
Lung Diseases, Interstitial	Lung Diseases	GWASDB_DG	23583980		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	33637690	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	GWASDB_DG	19915575, 21738487, 22438815, 24842889		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease	Parkinson disease	GWASCAT_DG	21738487		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease	Parkinson disease	Pubtator	32829096, 33637690	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary biliary cirrhosis	Biliary Cirrhosis	GWASDB_DG	22961000		★☆☆☆☆ Found in Text Mining only
Scleroderma Systemic	Systemic sclerosis	Pubtator	26792595	Associate	★☆☆☆☆ Found in Text Mining only