Q8IUH8 (SPP2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal peptide peptidase-like 2C
Short name=SPP-like 2C
Short name=SPPL2c
EC=3.4.23.-

Alternative name(s):
Intramembrane protease 5
Short name=IMP-5

Gene names

Name:	SPPL2C
Synonyms:	IMP5

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	684 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Intramembrane-cleaving aspartic protease (I-CLiP) that may be able to cleave type II membrane signal peptides in the hydrophobic plane of the membrane By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Probable. Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.5.
Tissue specificity	Ubiquitous. Ref.4
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.
Post-translational modification	Glycosylated. Ref.4
Sequence similarities	Belongs to the peptidase A22B family. Contains 1 PA (protease associated) domain.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to cytosolic side of endoplasmic reticulum membrane Inferred from direct assay Ref.4. Source: UniProtKB integral to lumenal side of endoplasmic reticulum membrane Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	aspartic-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 684	663	Signal peptide peptidase-like 2C		PRO_0000314797
Regions
	Topological domain	22 – 186	165	Lumenal Potential
	Transmembrane	187 – 207	21	Helical; Potential
	Topological domain	208 – 253	46	Cytoplasmic Potential
	Transmembrane	254 – 274	21	Helical; Potential
	Topological domain	275 – 276	2	Lumenal Potential
	Transmembrane	277 – 297	21	Helical; Potential
	Topological domain	298 – 319	22	Cytoplasmic Potential
	Transmembrane	320 – 340	21	Helical; Potential
	Topological domain	341 – 346	6	Lumenal Potential
	Transmembrane	347 – 365	19	Helical; Potential
	Topological domain	366 – 376	11	Cytoplasmic Potential
	Transmembrane	377 – 397	21	Helical; Potential
	Topological domain	398 – 439	42	Lumenal Potential
	Transmembrane	440 – 460	21	Helical; Potential
	Topological domain	461 – 472	12	Cytoplasmic Potential
	Transmembrane	473 – 493	21	Helical; Potential
	Topological domain	494 – 495	2	Lumenal Potential
	Transmembrane	496 – 516	21	Helical; Potential
	Topological domain	517 – 684	168	Cytoplasmic Potential
	Domain	83 – 163	81	PA
	Motif	499 – 501	3	PAL
Sites
	Active site	386	1	By similarity
	Active site	448	1	By similarity
Amino acid modifications
	Glycosylation	100	1	N-linked (GlcNAc...) Probable
Natural variations
	Natural variant	123	1	R → Q. Corresponds to variant rs17763658 [ dbSNP | Ensembl ].		VAR_038048
	Natural variant	303	1	R → H. Ref.1 Ref.3 Corresponds to variant rs242944 [ dbSNP | Ensembl ].		VAR_038049
	Natural variant	461	1	R → P. Corresponds to variant rs12185233 [ dbSNP | Ensembl ].		VAR_038050
	Natural variant	471	1	I → V. Corresponds to variant rs12185268 [ dbSNP | Ensembl ].		VAR_038051
	Natural variant	601	1	S → P. Corresponds to variant rs12373123 [ dbSNP | Ensembl ].		VAR_038052
	Natural variant	620	1	G → R. Corresponds to variant rs12373139 [ dbSNP | Ensembl ].		VAR_038053
	Natural variant	626	1	M → V. Ref.3		VAR_060590
	Natural variant	643	1	P → R. Corresponds to variant rs12373142 [ dbSNP | Ensembl ].		VAR_038054
	Natural variant	659	1	T → I. Corresponds to variant rs16940694 [ dbSNP | Ensembl ].		VAR_057147

Sequences

	Sequence		Length	Mass (Da)
	Q8IUH8 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: 578DA60509765667	FASTA	684	74,503
	10 20 30 40 50 60 MACLGFLLPV GFLLLISTVA GGKYGVAHVV SENWSKDYCI LFSSDYITLP RDLHHAPLLP 70 80 90 100 110 120 LYDGTKAPWC PGEDSPHQAQ LRSPSQRPLR QTTAMVMRGN CSFHTKGWLA QGQGAHGLLI 130 140 150 160 170 180 VSRVSDQQCS DTTLAPQDPR QPLADLTIPV AMLHYADMLD ILSHTRGEAV VRVAMYAPPE 190 200 210 220 230 240 PIIDYNMLVI FILAVGTVAA GGYWAGLTEA NRLQRRRARR GGGSGGHHQL QEAAAAEGAQ 250 260 270 280 290 300 KEDNEDIPVD FTPAMTGVVV TLSCSLMLLL YFFYDHFVYV TIGIFGLGAG IGLYSCLSPL 310 320 330 340 350 360 VCRLSLRQYQ RPPHSLWASL PLPLLLLASL CATVIIFWVA YRNEDRWAWL LQDTLGISYC 370 380 390 400 410 420 LFVLHRVRLP TLKNCSSFLL ALLAFDVFFV FVTPFFTKTG ESIMAQVALG PAESSSHERL 430 440 450 460 470 480 PMVLKVPRLR VSALTLCSQP FSILGFGDIV VPGFLVAYCC RFDVQVCSRQ IYFVACTVAY 490 500 510 520 530 540 AVGLLVTFMA MVLMQMGQPA LLYLVSSTLL TSLAVAACRQ ELSLFWTGQG RAKMCGLGCA 550 560 570 580 590 600 PSAGSRQKQE GAADAHTAST LERGTSRGAG DLDSNPGEDT TEIVTISENE ATNPEDRSDS 610 620 630 640 650 660 SEGWSDAHLD PNELPFIPPG ASEELMPLMP MAMLIPLMPL MPPPSELGHV HAQAQAHETG 670 680 LPWAGLHKRK GLKVRKSMST QAPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel class of polytopic proteins with domains associated with putative protease activity." Grigorenko A.P., Moliaka Y.K., Korovaitseva G.I., Rogaev E.I. Biokhimiia 67:826-834(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-303.
[2]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANTS HIS-303 AND VAL-626. Tissue: Testis.
[4]	"Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins." Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G., Martoglio B. J. Biol. Chem. 279:50790-50798(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, TOPOLOGY, TISSUE SPECIFICITY.
[5]	"SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production." Friedmann E., Hauben E., Maylandt K., Schleeger S., Vreugde S., Lichtenthaler S.F., Kuhn P.H., Stauffer D., Rovelli G., Martoglio B. Nat. Cell Biol. 8:843-848(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY169316 Genomic DNA. Translation: AAO12541.1. AC003662 Genomic DNA. No translation available. AC217770 Genomic DNA. No translation available. AC217771 Genomic DNA. No translation available. BC022041 mRNA. Translation: AAH22041.2. BC025401 mRNA. Translation: AAH25401.1.
IPI	IPI00103286.
RefSeq	NP_787078.2. NM_175882.2.
UniGene	Hs.144491.
3D structure databases
ProteinModelPortal	Q8IUH8.
ModBase	Search...
Protein family/group databases
MEROPS	A22.006.
Polymorphism databases
DMDM	269849676.
Proteomic databases
PaxDb	Q8IUH8.
PRIDE	Q8IUH8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000329196; ENSP00000332488; ENSG00000185294.
GeneID	162540.
KEGG	hsa:162540.
UCSC	uc010wka.2. human.
Organism-specific databases
CTD	162540.
GeneCards	GC17P043923.
H-InvDB	HIX0013905.
HGNC	HGNC:28902. SPPL2C.
HPA	HPA024444.
MIM	608284. gene.
neXtProt	NX_Q8IUH8.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG268366.
HOGENOM	HOG000231496.
HOVERGEN	HBG024193.
InParanoid	Q8IUH8.
KO	K14212.
OMA	LPTLKNC.
OrthoDB	EOG4Q2DF6.
Gene expression databases
Bgee	Q8IUH8.
Genevestigator	Q8IUH8.
Family and domain databases
InterPro	IPR006639. Peptidase_A22. IPR007369. Peptidase_A22B_SPP. IPR003137. Protease-assoc_domain. [Graphical view]
PANTHER	PTHR12174. PTHR12174. 1 hit.
Pfam	PF02225. PA. 1 hit. PF04258. Peptidase_A22B. 1 hit. [Graphical view]
SMART	SM00730. PSN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	162540.
NextBio	88197.
SOURCE	Search...

Entry information

Entry name

SPP2C_HUMAN

Accession

Primary (citable) accession number: Q8IUH8
Secondary accession number(s): Q8TC67, Q8WVZ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 67 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.