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Protein

Minor histocompatibility antigen H13

Gene

HM13

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein, resulting in the release of the fragment from the ER membrane into the cytoplasm. Required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides (PubMed:11714810). May be necessary for the removal of the signal peptide that remains attached to the hepatitis C virus core protein after the initial proteolytic processing of the polyprotein (PubMed:12145199). Involved in the intramembrane cleavage of the integral membrane protein PSEN1 (PubMed:12077416, PubMed:11714810, PubMed:14741365). Cleaves the integral membrane protein XBP1 isoform 1 in a DERL1/RNF139-dependent manner (PubMed:25239945). May play a role in graft rejection (By similarity).By similarity5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei219By similarity1
Active sitei265By similarity1

GO - Molecular functioni

  • aspartic endopeptidase activity, intramembrane cleaving Source: UniProtKB
  • peptidase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • membrane protein proteolysis Source: UniProtKB
  • membrane protein proteolysis involved in retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
  • protein homotetramerization Source: ParkinsonsUK-UCL

Keywordsi

Molecular functionHydrolase, Protease

Protein family/group databases

MEROPSiA22.003

Names & Taxonomyi

Protein namesi
Recommended name:
Minor histocompatibility antigen H13 (EC:3.4.23.-)
Alternative name(s):
Intramembrane protease 1
Short name:
IMP-1
Short name:
IMPAS-1
Short name:
hIMP1
Presenilin-like protein 3
Signal peptide peptidase
Gene namesi
Name:HM13
Synonyms:H13, IMP1, PSL3, SPP
ORF Names:MSTP086
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi

Organism-specific databases

EuPathDBiHostDB:ENSG00000101294.16
HGNCiHGNC:16435 HM13
MIMi607106 gene
neXtProtiNX_Q8TCT9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 31Lumenal2 PublicationsAdd BLAST31
Transmembranei32 – 52HelicalSequence analysisAdd BLAST21
Topological domaini53 – 77CytoplasmicSequence analysisAdd BLAST25
Transmembranei78 – 98HelicalSequence analysisAdd BLAST21
Topological domaini99 – 100LumenalSequence analysis2
Transmembranei101 – 121HelicalSequence analysisAdd BLAST21
Topological domaini122 – 157CytoplasmicSequence analysisAdd BLAST36
Transmembranei158 – 178HelicalSequence analysisAdd BLAST21
Topological domaini179 – 181LumenalSequence analysis3
Transmembranei182 – 202HelicalSequence analysisAdd BLAST21
Topological domaini203 – 209CytoplasmicSequence analysis7
Transmembranei210 – 230HelicalSequence analysisAdd BLAST21
Topological domaini231 – 256Lumenal1 PublicationAdd BLAST26
Transmembranei257 – 277HelicalSequence analysisAdd BLAST21
Topological domaini278 – 290CytoplasmicSequence analysisAdd BLAST13
Transmembranei291 – 311HelicalSequence analysisAdd BLAST21
Topological domaini312 – 314LumenalSequence analysis3
Transmembranei315 – 335HelicalSequence analysisAdd BLAST21
Topological domaini336 – 377Cytoplasmic1 PublicationAdd BLAST42

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10N → Q: Abolishes N-glycosylation; when associated with Q-20. 1 Publication1
Mutagenesisi20N → Q: Abolishes N-glycosylation; when associated with Q-10. 1 Publication1
Mutagenesisi219D → A: Abolishes proteolysis of PSEN1. 1 Publication1
Mutagenesisi264G → A: No effect on proteolysis of PSEN1. 1 Publication1
Mutagenesisi265D → A: No effect on inhibitor binding; abolishes catalytic activity. Abolishes proteolysis of PSEN1. Abolishes proteolysis of XBP1 isoform 1 and increases interaction with XBP1 isoform 1. 3 Publications1
Mutagenesisi317P → L: Abolishes proteolysis of PSEN1. 1 Publication1

Organism-specific databases

DisGeNETi81502
OpenTargetsiENSG00000101294
PharmGKBiPA29314

Polymorphism and mutation databases

DMDMi25008563

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000739071 – 377Minor histocompatibility antigen H13Add BLAST377

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi20N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei367PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.3 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8TCT9
MaxQBiQ8TCT9
PeptideAtlasiQ8TCT9
PRIDEiQ8TCT9
TopDownProteomicsiQ8TCT9-1 [Q8TCT9-1]
Q8TCT9-5 [Q8TCT9-5]

PTM databases

iPTMnetiQ8TCT9
PhosphoSitePlusiQ8TCT9
SwissPalmiQ8TCT9

Expressioni

Tissue specificityi

Widely expressed with highest levels in kidney, liver, placenta, lung, leukocytes and small intestine and reduced expression in heart and skeletal muscle. Expressed abundantly in the CNS with highest levels in thalamus and medulla.2 Publications

Gene expression databases

BgeeiENSG00000101294
ExpressionAtlasiQ8TCT9 baseline and differential
GenevisibleiQ8TCT9 HS

Organism-specific databases

HPAiHPA045089
HPA056062

Interactioni

Subunit structurei

Monomer (PubMed:15385547, PubMed:15998642). Homodimer (PubMed:15385547, PubMed:15998642). Interacts with RNF139 (PubMed:19720873, PubMed:25239945). Interacts with DERL1 and XBP1 isoform 1 (PubMed:25239945).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi123505, 28 interactors
IntActiQ8TCT9, 27 interactors
MINTiQ8TCT9

Structurei

3D structure databases

ProteinModelPortaliQ8TCT9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi317 – 319PAL3

Domaini

The first transmembrane domain may act as a type I signal anchor (PubMed:12077416, PubMed:15385547). The PAL motif is required for normal active site conformation (By similarity).By similarity2 Publications

Sequence similaritiesi

Belongs to the peptidase A22B family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00530000062920
HOVERGENiHBG024161
InParanoidiQ8TCT9
KOiK09595
OMAiWWVFGTE
OrthoDBiEOG091G0AWL
PhylomeDBiQ8TCT9
TreeFamiTF105854

Family and domain databases

InterProiView protein in InterPro
IPR007369 Peptidase_A22B_SPP
IPR006639 Preselin/SPP
PANTHERiPTHR12174 PTHR12174, 1 hit
PfamiView protein in Pfam
PF04258 Peptidase_A22B, 1 hit
SMARTiView protein in SMART
SM00730 PSN, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TCT9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDSALSDPHN GSAEAGGPTN STTRPPSTPE GIALAYGSLL LMALLPIFFG
60 70 80 90 100
ALRSVRCARG KNASDMPETI TSRDAARFPI IASCTLLGLY LFFKIFSQEY
110 120 130 140 150
INLLLSMYFF VLGILALSHT ISPFMNKFFP ASFPNRQYQL LFTQGSGENK
160 170 180 190 200
EEIINYEFDT KDLVCLGLSS IVGVWYLLRK HWIANNLFGL AFSLNGVELL
210 220 230 240 250
HLNNVSTGCI LLGGLFIYDV FWVFGTNVMV TVAKSFEAPI KLVFPQDLLE
260 270 280 290 300
KGLEANNFAM LGLGDVVIPG IFIALLLRFD ISLKKNTHTY FYTSFAAYIF
310 320 330 340 350
GLGLTIFIMH IFKHAQPALL YLVPACIGFP VLVALAKGEV TEMFSYEESN
360 370
PKDPAAVTES KEGTEASASK GLEKKEK
Length:377
Mass (Da):41,488
Last modified:June 1, 2002 - v1
Checksum:i322D231B52B33118
GO
Isoform 2 (identifier: Q8TCT9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     347-347: E → ESSAEILPHTPRLTHFPTVSGSPASLADSMQQKLAGPRRRRPQNPSAIYE

Show »
Length:426
Mass (Da):46,825
Checksum:i269AD5CC99982845
GO
Isoform 4 (identifier: Q8TCT9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     348-377: ESNPKDPAAVTESKEGTEASASKGLEKKEK → SSAEILPHTP...RRRPQNPSAM

Show »
Length:394
Mass (Da):43,423
Checksum:i9BEC3A1C9B605D48
GO
Isoform 5 (identifier: Q8TCT9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     181-222: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:335
Mass (Da):36,814
Checksum:iD22777AF67B3720B
GO

Sequence cautioni

The sequence AAQ13609 differs from that shown. Reason: Frameshift at positions 320, 329, 330 and 358.Curated
The sequence BAC11138 differs from that shown. Intron retention.Curated
The sequence CAI19152 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI20173 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti132S → N AA sequence (PubMed:12077416).Curated1
Sequence conflicti150K → R in BAC11519 (PubMed:14702039).Curated1
Sequence conflicti159D → A AA sequence (PubMed:12077416).Curated1
Sequence conflicti235S → F in AAH08938 (PubMed:15489334).Curated1
Sequence conflicti235S → F in AAH08959 (PubMed:15489334).Curated1
Sequence conflicti295F → Y in AAQ13609 (Ref. 7) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014274259A → P. Corresponds to variant dbSNP:rs1044419Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015082181 – 222Missing in isoform 5. CuratedAdd BLAST42
Alternative sequenceiVSP_005196347E → ESSAEILPHTPRLTHFPTVS GSPASLADSMQQKLAGPRRR RPQNPSAIYE in isoform 2. 1 Publication1
Alternative sequenceiVSP_015083348 – 377ESNPK…EKKEK → SSAEILPHTPRLTHFPTVSG SPASLADSMQQKLAGPRRRR PQNPSAM in isoform 4. 2 PublicationsAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ420895 mRNA Translation: CAD13132.1
AF515663 mRNA Translation: AAN77099.1
AY169310 mRNA Translation: AAO12535.1
AY169311 mRNA Translation: AAO12536.1
AY169312 mRNA Translation: AAO12537.1
DQ168450 mRNA Translation: ABA56163.1
AJ345029 mRNA Translation: CAC87790.1
AF483215 mRNA Translation: AAM22076.1
AF172086 mRNA Translation: AAQ13609.1 Frameshift.
AK074686 mRNA Translation: BAC11138.1 Sequence problems.
AK075283 mRNA Translation: BAC11519.1
AK314410 mRNA Translation: BAG37032.1
AL110115, AL121751 Genomic DNA Translation: CAI20173.1 Sequence problems.
AL110115, AL121751 Genomic DNA Translation: CAI20174.1
AL110115, AL121751 Genomic DNA Translation: CAI20175.2
AL121751, AL110115 Genomic DNA Translation: CAI19152.1 Sequence problems.
AL121751, AL110115 Genomic DNA Translation: CAI19153.1
AL121751, AL110115 Genomic DNA Translation: CAI19154.2
CH471077 Genomic DNA Translation: EAW76436.1
CH471077 Genomic DNA Translation: EAW76437.1
CH471077 Genomic DNA Translation: EAW76435.1
CH471077 Genomic DNA Translation: EAW76438.1
BC008938 mRNA Translation: AAH08938.1
BC008959 mRNA Translation: AAH08959.1
BC062595 mRNA Translation: AAH62595.1
CCDSiCCDS13182.1 [Q8TCT9-1]
CCDS13183.1 [Q8TCT9-4]
CCDS42861.1 [Q8TCT9-2]
RefSeqiNP_110416.1, NM_030789.3 [Q8TCT9-1]
NP_848695.1, NM_178580.2 [Q8TCT9-4]
NP_848696.1, NM_178581.2 [Q8TCT9-2]
NP_848697.1, NM_178582.2
UniGeneiHs.373741

Genome annotation databases

EnsembliENST00000335574; ENSP00000335294; ENSG00000101294 [Q8TCT9-4]
ENST00000340852; ENSP00000343032; ENSG00000101294 [Q8TCT9-1]
ENST00000398174; ENSP00000381237; ENSG00000101294 [Q8TCT9-2]
GeneIDi81502
KEGGihsa:81502
UCSCiuc002wwb.3 human [Q8TCT9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHM13_HUMAN
AccessioniPrimary (citable) accession number: Q8TCT9
Secondary accession number(s): B2RAY5
, E1P5L3, Q15K36, Q540H8, Q5JWP2, Q5JWP3, Q5JWP4, Q5JWP5, Q7Z4F2, Q86Y35, Q95H87, Q9H110, Q9H111
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: June 1, 2002
Last modified: May 23, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

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