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Q8IUH8 (SPP2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length684 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 684663Signal peptide peptidase-like 2C
PRO_0000314797

Regions

Topological domain22 – 186165Lumenal Potential
Transmembrane187 – 20721Helical; Potential
Topological domain208 – 25346Cytoplasmic Potential
Transmembrane254 – 27421Helical; Potential
Topological domain275 – 2762Lumenal Potential
Transmembrane277 – 29721Helical; Potential
Topological domain298 – 31922Cytoplasmic Potential
Transmembrane320 – 34021Helical; Potential
Topological domain341 – 3466Lumenal Potential
Transmembrane347 – 36519Helical; Potential
Topological domain366 – 37611Cytoplasmic Potential
Transmembrane377 – 39721Helical; Potential
Topological domain398 – 43942Lumenal Potential
Transmembrane440 – 46021Helical; Potential
Topological domain461 – 47212Cytoplasmic Potential
Transmembrane473 – 49321Helical; Potential
Topological domain494 – 4952Lumenal Potential
Transmembrane496 – 51621Helical; Potential
Topological domain517 – 684168Cytoplasmic Potential
Domain83 – 16381PA
Motif499 – 5013PAL

Sites

Active site3861 By similarity
Active site4481 By similarity

Amino acid modifications

Glycosylation1001N-linked (GlcNAc...) Probable

Natural variations

Natural variant1231R → Q.
Corresponds to variant rs17763658 [ dbSNP | Ensembl ].
VAR_038048
Natural variant3031R → H. Ref.1 Ref.3
Corresponds to variant rs242944 [ dbSNP | Ensembl ].
VAR_038049
Natural variant4611R → P.
Corresponds to variant rs12185233 [ dbSNP | Ensembl ].
VAR_038050
Natural variant4711I → V.
Corresponds to variant rs12185268 [ dbSNP | Ensembl ].
VAR_038051
Natural variant6011S → P.
Corresponds to variant rs12373123 [ dbSNP | Ensembl ].
VAR_038052
Natural variant6201G → R.
Corresponds to variant rs12373139 [ dbSNP | Ensembl ].
VAR_038053
Natural variant6261M → V. Ref.3
VAR_060590
Natural variant6431P → R.
Corresponds to variant rs12373142 [ dbSNP | Ensembl ].
VAR_038054
Natural variant6591T → I.
Corresponds to variant rs16940694 [ dbSNP | Ensembl ].
VAR_057147

Sequences

Sequence LengthMass (Da)Tools
Q8IUH8 [UniParc].

Last modified November 24, 2009. Version 3.
Checksum: 578DA60509765667

FASTA68474,503
        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 

« Hide

References

« Hide '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.
Biochemistry (Mosc.) 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. expand/collapse author list , 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.
CCDSCCDS32673.1.
RefSeqNP_787078.2. NM_175882.2.
UniGeneHs.144491.

3D structure databases

ProteinModelPortalQ8IUH8.
SMRQ8IUH8. Positions 89-175.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSA22.006.

Polymorphism databases

DMDM269849676.

Proteomic databases

PaxDbQ8IUH8.
PRIDEQ8IUH8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329196; ENSP00000332488; ENSG00000185294.
GeneID162540.
KEGGhsa:162540.
UCSCuc010wka.2. human.

Organism-specific databases

CTD162540.
GeneCardsGC17P043923.
H-InvDBHIX0013905.
HGNCHGNC:28902. SPPL2C.
HPAHPA024444.
MIM608284. gene.
neXtProtNX_Q8IUH8.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG268366.
HOGENOMHOG000231496.
HOVERGENHBG024193.
InParanoidQ8IUH8.
KOK14212.
OMAILWVAYR.
OrthoDBEOG769ZJ4.
PhylomeDBQ8IUH8.
TreeFamTF319186.

Gene expression databases

BgeeQ8IUH8.
GenevestigatorQ8IUH8.

Family and domain databases

InterProIPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
IPR003137. Protease-assoc_domain.
[Graphical view]
PANTHERPTHR12174. PTHR12174. 1 hit.
PfamPF02225. PA. 1 hit.
PF04258. Peptidase_A22B. 1 hit.
[Graphical view]
SMARTSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi162540.
NextBio88197.
PROQ8IUH8.
SOURCESearch...

Entry information

Entry nameSPP2C_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 76 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM