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Protein

Alpha-protein kinase 1

Gene

ALPK1

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

Functioni

Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity (PubMed:28877472, PubMed:28222186, PubMed:30111836). Specifically recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria (PubMed:30111836). ADP-Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering proinflammatory NF-kappa-B signaling (PubMed:30111836). May be involved in monosodium urate monohydrate (MSU)-induced inflammation by mediating phosphorylation of unconventional myosin MYO9A (PubMed:27169898). May also play a role in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A (PubMed:15883161).5 Publications

Caution

D-glycero-beta-D-manno-heptose 1,7-bisphosphate (HBP) was initially thought to constitute the bacterial pathogen-associated molecular pattern metabolite (PAMP) triggering the ALPK1-TIFA innate immunune response (PubMed:28877472, PubMed:28222186). It was however shown that ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) constitutes the main PAMP that activates the kinase activity of ALPK1 (PubMed:30111836).3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Activity regulationi

Serine/threonine-protein kinase activity is stimulated upon ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose)-binding.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei61ADP-D-glycero-beta-D-manno-heptose1 Publication1
Binding sitei67ADP-D-glycero-beta-D-manno-heptose1 Publication1
Binding sitei116ADP-D-glycero-beta-D-manno-heptose1 Publication1
Binding sitei231ADP-D-glycero-beta-D-manno-heptose1 Publication1
Binding sitei233ADP-D-glycero-beta-D-manno-heptose1 Publication1
Binding sitei295ADP-D-glycero-beta-D-manno-heptose1 Publication1

GO - Molecular functioni

  • ATP binding Source: InterPro
  • monosaccharide binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processImmunity, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-protein kinase 11 Publication (EC:2.7.11.12 Publications)
Alternative name(s):
Chromosome 4 kinase1 Publication
Lymphocyte alpha-protein kinaseImported
Gene namesi
Name:ALPK11 PublicationImported
Synonyms:KIAA15271 Publication, LAKImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000073331.17
HGNCiHGNC:20917 ALPK1
MIMi607347 gene
neXtProtiNX_Q96QP1

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

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67Q → A: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity; when associated with A-231. 1 Publication1
Mutagenesisi116R → A: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi150R → A: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi153R → A: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi231D → A: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity; when associated with A-67. 1 Publication1
Mutagenesisi233K → A: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi237T → E: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity; when associated with K-295. 1 Publication1
Mutagenesisi295F → K: Impaired ADP-D-glycero-beta-D-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity; when associated with E-237. 1 Publication1
Mutagenesisi1067K → M: Abolishes the serine/threonine-protein kinase and ability to initiate the innate immune response. 1 Publication1

Organism-specific databases

DisGeNETi80216
OpenTargetsiENSG00000073331
PharmGKBiPA134891785

Polymorphism and mutation databases

BioMutaiALPK1
DMDMi308153632

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002600281 – 1244Alpha-protein kinase 1Add BLAST1244

Proteomic databases

EPDiQ96QP1
MaxQBiQ96QP1
PaxDbiQ96QP1
PeptideAtlasiQ96QP1
PRIDEiQ96QP1
ProteomicsDBi77886

PTM databases

iPTMnetiQ96QP1
PhosphoSitePlusiQ96QP1

Expressioni

Tissue specificityi

Highly expressed in liver.1 Publication

Gene expression databases

BgeeiENSG00000073331 Expressed in 205 organ(s), highest expression level in amniotic fluid
CleanExiHS_ALPK1
ExpressionAtlasiQ96QP1 baseline and differential
GenevisibleiQ96QP1 HS

Organism-specific databases

HPAiHPA027435
HPA027443

Interactioni

Protein-protein interaction databases

BioGridi123183, 6 interactors
IntActiQ96QP1, 2 interactors
STRINGi9606.ENSP00000177648

Structurei

Secondary structure

11244
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96QP1
SMRiQ96QP1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1017 – 1237Alpha-type protein kinasePROSITE-ProRule annotationAdd BLAST221

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni150 – 153ADP-D-glycero-beta-D-manno-heptose binding1 Publication4
Regioni236 – 237ADP-D-glycero-beta-D-manno-heptose binding1 Publication2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi105 – 109Poly-Ala5
Compositional biasi921 – 960Ser-richAdd BLAST40

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IFN0 Eukaryota
ENOG4110KQR LUCA
GeneTreeiENSGT00800000124135
HOGENOMiHOG000169279
HOVERGENiHBG079770
InParanoidiQ96QP1
KOiK08868
OMAiHSVDQKD
OrthoDBiEOG091G00VW
PhylomeDBiQ96QP1
TreeFamiTF316085

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR004166 MHCK_EF2_kinase
PfamiView protein in Pfam
PF02816 Alpha_kinase, 1 hit
SMARTiView protein in SMART
SM00811 Alpha_kinase, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51158 ALPHA_KINASE, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96QP1-1) [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
MNNQKVVAVL LQECKQVLDQ LLLEAPDVSE EDKSEDQRCR ALLPSELRTL
60 70 80 90 100
IQEAKEMKWP FVPEKWQYKQ AVGPEDKTNL KDVIGAGLQQ LLASLRASIL
110 120 130 140 150
ARDCAAAAAI VFLVDRFLYG LDVSGKLLQV AKGLHKLQPA TPIAPQVVIR
160 170 180 190 200
QARISVNSGK LLKAEYILSS LISNNGATGT WLYRNESDKV LVQSVCIQIR
210 220 230 240 250
GQILQKLGMW YEAAELIWAS IVGYLALPQP DKKGLSTSLG ILADIFVSMS
260 270 280 290 300
KNDYEKFKNN PQINLSLLKE FDHHLLSAAE ACKLAAAFSA YTPLFVLTAV
310 320 330 340 350
NIRGTCLLSY SSSNDCPPEL KNLHLCEAKE AFEIGLLTKR DDEPVTGKQE
360 370 380 390 400
LHSFVKAAFG LTTVHRRLHG ETGTVHAASQ LCKEAMGKLY NFSTSSRSQD
410 420 430 440 450
REALSQEVMS VIAQVKEHLQ VQSFSNVDDR SYVPESFECR LDKLILHGQG
460 470 480 490 500
DFQKILDTYS QHHTSVCEVF ESDCGNNKNE QKDAKTGVCI TALKTEIKNI
510 520 530 540 550
DTVSTTQEKP HCQRDTGISS SLMGKNVQRE LRRGGRRNWT HSDAFRVSLD
560 570 580 590 600
QDVETETEPS DYSNGEGAVF NKSLSGSQTS SAWSNLSGFS SSASWEEVNY
610 620 630 640 650
HVDDRSARKE PGKEHLVDTQ CSTALSEELE NDREGRAMHS LHSQLHDLSL
660 670 680 690 700
QEPNNDNLEP SQNQPQQQMP LTPFSPHNTP GIFLAPGAGL LEGAPEGIQE
710 720 730 740 750
VRNMGPRNTS AHSRPSYRSA SWSSDSGRPK NMGTHPSVQK EEAFEIIVEF
760 770 780 790 800
PETNCDVKDR QGKEQGEEIS ERGAGPTFKA SPSWVDPEGE TAESTEDAPL
810 820 830 840 850
DFHRVLHNSL GNISMLPCSS FTPNWPVQNP DSRKSGGPVA EQGIDPDAST
860 870 880 890 900
VDEEGQLLDS MDVPCTNGHG SHRLCILRQP PGQRAETPNS SVSGNILFPV
910 920 930 940 950
LSEDCTTTEE GNQPGNMLNC SQNSSSSSVW WLKSPAFSSG SSEGDSPWSY
960 970 980 990 1000
LNSSGSSWVS LPGKMRKEIL EARTLQPDDF EKLLAGVRHD WLFQRLENTG
1010 1020 1030 1040 1050
VFKPSQLHRA HSALLLKYSK KSELWTAQET IVYLGDYLTV KKKGRQRNAF
1060 1070 1080 1090 1100
WVHHLHQEEI LGRYVGKDYK EQKGLWHHFT DVERQMTAQH YVTEFNKRLY
1110 1120 1130 1140 1150
EQNIPTQIFY IPSTILLILE DKTIKGCISV EPYILGEFVK LSNNTKVVKT
1160 1170 1180 1190 1200
EYKATEYGLA YGHFSYEFSN HRDVVVDLQG WVTGNGKGLI YLTDPQIHSV
1210 1220 1230 1240
DQKVFTTNFG KRGIFYFFNN QHVECNEICH RLSLTRPSME KPCT
Length:1,244
Mass (Da):138,861
Last modified:October 5, 2010 - v3
Checksum:i857D353D159A1630
GO
Isoform 2 (identifier: Q96QP1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-92: MNNQKVVAVL...VIGAGLQQLL → MCRKRTRARTSAAE

Note: No experimental confirmation available.
Show »
Length:1,166
Mass (Da):129,951
Checksum:i1996AB197A4DDEEC
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4E0R2B4E0R2_HUMAN
Alpha-protein kinase 1
ALPK1
168Annotation score:
B3KUH8B3KUH8_HUMAN
Alpha-protein kinase 1
ALPK1
304Annotation score:
D6RDN6D6RDN6_HUMAN
Alpha-protein kinase 1
ALPK1
109Annotation score:
D6RB29D6RB29_HUMAN
Alpha-protein kinase 1
ALPK1
133Annotation score:

Sequence cautioni

The sequence BAC85140 differs from that shown. Intron retention.Curated
The sequence BAC85140 differs from that shown. Reason: Frameshift at positions 208 and 1022.Curated
The sequence BAC85140 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BC060780 differs from that shown. Reason: Frameshift at position 1044.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti83V → L in BAC85140 (Ref. 5) Curated1
Sequence conflicti577S → G in BAG65473 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04151167Q → R1 PublicationCorresponds to variant dbSNP:rs33943680Ensembl.1
Natural variantiVAR_028982175N → D1 PublicationCorresponds to variant dbSNP:rs6533616Ensembl.1
Natural variantiVAR_041512292T → M1 PublicationCorresponds to variant dbSNP:rs34120296Ensembl.1
Natural variantiVAR_041513320L → M1 Publication1
Natural variantiVAR_041514339K → E in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041515383K → E1 PublicationCorresponds to variant dbSNP:rs147641444Ensembl.1
Natural variantiVAR_028983565G → D5 PublicationsCorresponds to variant dbSNP:rs2074388Ensembl.1
Natural variantiVAR_028984642H → R5 PublicationsCorresponds to variant dbSNP:rs13148353Ensembl.1
Natural variantiVAR_041516660P → L1 PublicationCorresponds to variant dbSNP:rs35389530Ensembl.1
Natural variantiVAR_041517681G → D2 PublicationsCorresponds to variant dbSNP:rs35519493Ensembl.1
Natural variantiVAR_028985732M → I5 PublicationsCorresponds to variant dbSNP:rs2074379Ensembl.1
Natural variantiVAR_028986861M → T5 PublicationsCorresponds to variant dbSNP:rs11726117Ensembl.1
Natural variantiVAR_028987870G → S1 PublicationCorresponds to variant dbSNP:rs2074380Ensembl.1
Natural variantiVAR_041518873R → I1 PublicationCorresponds to variant dbSNP:rs34946272Ensembl.1
Natural variantiVAR_041519910E → D1 PublicationCorresponds to variant dbSNP:rs35308602Ensembl.1
Natural variantiVAR_028988916N → D1 PublicationCorresponds to variant dbSNP:rs2074381Ensembl.1
Natural variantiVAR_041520935P → L1 PublicationCorresponds to variant dbSNP:rs34780600Ensembl.1
Natural variantiVAR_0577411008H → P. Corresponds to variant dbSNP:rs34079946Ensembl.1
Natural variantiVAR_0415211084R → Q1 PublicationCorresponds to variant dbSNP:rs34677416Ensembl.1
Natural variantiVAR_0415221117L → P1 PublicationCorresponds to variant dbSNP:rs35756863Ensembl.1
Natural variantiVAR_0415231160A → G1 PublicationCorresponds to variant dbSNP:rs55696324Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0447351 – 92MNNQK…LQQLL → MCRKRTRARTSAAE in isoform 2. 1 PublicationAdd BLAST92

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY044164 mRNA Translation: AAK94675.1
AK304708 mRNA Translation: BAG65473.1
AC004049 Genomic DNA No translation available.
AC109347 Genomic DNA No translation available.
BC060780 mRNA No translation available.
AK131090 mRNA Translation: BAC85140.1 Sequence problems.
AB040960 mRNA Translation: BAA96051.1
AB075877 mRNA Translation: BAD38659.1
CCDSiCCDS3697.1 [Q96QP1-1]
CCDS58923.1 [Q96QP1-2]
RefSeqiNP_001095876.1, NM_001102406.1 [Q96QP1-1]
NP_001240813.1, NM_001253884.1 [Q96QP1-2]
NP_079420.3, NM_025144.3 [Q96QP1-1]
UniGeneiHs.652825

Genome annotation databases

EnsembliENST00000177648; ENSP00000177648; ENSG00000073331 [Q96QP1-1]
ENST00000458497; ENSP00000398048; ENSG00000073331 [Q96QP1-1]
ENST00000504176; ENSP00000426044; ENSG00000073331 [Q96QP1-2]
GeneIDi80216
KEGGihsa:80216
UCSCiuc003ian.5 human [Q96QP1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY044164 mRNA Translation: AAK94675.1
AK304708 mRNA Translation: BAG65473.1
AC004049 Genomic DNA No translation available.
AC109347 Genomic DNA No translation available.
BC060780 mRNA No translation available.
AK131090 mRNA Translation: BAC85140.1 Sequence problems.
AB040960 mRNA Translation: BAA96051.1
AB075877 mRNA Translation: BAD38659.1
CCDSiCCDS3697.1 [Q96QP1-1]
CCDS58923.1 [Q96QP1-2]
RefSeqiNP_001095876.1, NM_001102406.1 [Q96QP1-1]
NP_001240813.1, NM_001253884.1 [Q96QP1-2]
NP_079420.3, NM_025144.3 [Q96QP1-1]
UniGeneiHs.652825

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5Z2CX-ray2.59A/B/C/D/E/F/G/H/I1-446[»]
ProteinModelPortaliQ96QP1
SMRiQ96QP1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123183, 6 interactors
IntActiQ96QP1, 2 interactors
STRINGi9606.ENSP00000177648

PTM databases

iPTMnetiQ96QP1
PhosphoSitePlusiQ96QP1

Polymorphism and mutation databases

BioMutaiALPK1
DMDMi308153632

Proteomic databases

EPDiQ96QP1
MaxQBiQ96QP1
PaxDbiQ96QP1
PeptideAtlasiQ96QP1
PRIDEiQ96QP1
ProteomicsDBi77886

Protocols and materials databases

DNASUi80216
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000177648; ENSP00000177648; ENSG00000073331 [Q96QP1-1]
ENST00000458497; ENSP00000398048; ENSG00000073331 [Q96QP1-1]
ENST00000504176; ENSP00000426044; ENSG00000073331 [Q96QP1-2]
GeneIDi80216
KEGGihsa:80216
UCSCiuc003ian.5 human [Q96QP1-1]

Organism-specific databases

CTDi80216
DisGeNETi80216
EuPathDBiHostDB:ENSG00000073331.17
GeneCardsiALPK1
H-InvDBiHIX0004446
HGNCiHGNC:20917 ALPK1
HPAiHPA027435
HPA027443
MIMi607347 gene
neXtProtiNX_Q96QP1
OpenTargetsiENSG00000073331
PharmGKBiPA134891785
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFN0 Eukaryota
ENOG4110KQR LUCA
GeneTreeiENSGT00800000124135
HOGENOMiHOG000169279
HOVERGENiHBG079770
InParanoidiQ96QP1
KOiK08868
OMAiHSVDQKD
OrthoDBiEOG091G00VW
PhylomeDBiQ96QP1
TreeFamiTF316085

Miscellaneous databases

ChiTaRSiALPK1 human
GeneWikiiALPK1
GenomeRNAii80216
PROiPR:Q96QP1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073331 Expressed in 205 organ(s), highest expression level in amniotic fluid
CleanExiHS_ALPK1
ExpressionAtlasiQ96QP1 baseline and differential
GenevisibleiQ96QP1 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR004166 MHCK_EF2_kinase
PfamiView protein in Pfam
PF02816 Alpha_kinase, 1 hit
SMARTiView protein in SMART
SM00811 Alpha_kinase, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51158 ALPHA_KINASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiALPK1_HUMAN
AccessioniPrimary (citable) accession number: Q96QP1
Secondary accession number(s): B4E3G1
, F5H138, Q68CI9, Q6P9F9, Q6ZNK4, Q9P201
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: October 5, 2010
Last modified: November 7, 2018
This is version 129 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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