UniProtKB - P22413 (ENPP1_HUMAN)
Protein
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Gene
ENPP1
Organism
Homo sapiens (Human)
Status
Functioni
Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:11004006). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:27467858, PubMed:8001561, PubMed:25344812). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:27467858, PubMed:8001561). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity and function (PubMed:10615944). Also involved in melanogenesis (PubMed:28964717). Also able to hydrolyze 2'-3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2'-3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2'-3'-cGAMP hydrolysis is therefore unclear (PubMed:25344812). Not able to hydrolyze the 2'-3'-cGAMP linkage isomer 3'-3'-cGAMP (PubMed:25344812).By similarity1 Publication5 Publications
Caution
It is uncertain whether Met-1 or Met-53 is the initiator.Curated
Catalytic activityi
- a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-phosphate + diphosphate + H+2 PublicationsEC:3.6.1.92 PublicationsThis reaction proceeds in the forward1 Publication direction.
- a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-deoxyribonucleoside 5'-phosphate + diphosphate + H+1 PublicationEC:3.6.1.91 Publication
- This reaction proceeds in the forward1 Publication direction.
- Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.1 Publication EC:3.1.4.1
Cofactori
Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity
Activity regulationi
At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.By similarity
Kineticsi
Kcat is 4 sec(-1) with 2'-3'-cGAMP (PubMed:25344812). Kcat is 12 sec(-1) with ATP (PubMed:25344812).1 Publication
- KM=15 µM for 2'-3'-cGAMP1 Publication
- KM=20 µM for ATP1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 218 | Zinc 1; catalyticBy similarity | 1 | |
Active sitei | 256 | AMP-threonine intermediateBy similarity | 1 | |
Metal bindingi | 256 | Zinc 1; catalyticBy similarity | 1 | |
Binding sitei | 277 | SubstrateBy similarity | 1 | |
Binding sitei | 295 | SubstrateBy similarity | 1 | |
Binding sitei | 326 | SubstrateBy similarity | 1 | |
Binding sitei | 340 | SubstrateBy similarity | 1 | |
Metal bindingi | 376 | Zinc 2; catalyticBy similarity | 1 | |
Metal bindingi | 380 | Zinc 2; via tele nitrogen; catalyticBy similarity | 1 | |
Binding sitei | 380 | Substrate 2'-3'-cGAMPBy similarity | 1 | |
Metal bindingi | 423 | Zinc 1; catalyticBy similarity | 1 | |
Metal bindingi | 424 | Zinc 1; via tele nitrogen; catalyticBy similarity | 1 | |
Binding sitei | 532 | Substrate 2'-3'-cGAMPBy similarity | 1 | |
Metal bindingi | 535 | Zinc 2; via tele nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 800 | CalciumBy similarity | 1 | |
Metal bindingi | 802 | CalciumBy similarity | 1 | |
Metal bindingi | 804 | CalciumBy similarity | 1 | |
Metal bindingi | 806 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 808 | CalciumBy similarity | 1 | |
Sitei | 915 | Essential for catalytic activityBy similarity | 1 |
GO - Molecular functioni
- 3'-phosphoadenosine 5'-phosphosulfate binding Source: BHF-UCL
- ATP binding Source: BHF-UCL
- calcium ion binding Source: UniProtKB
- cyclic-GMP-AMP hydrolase activity Source: UniProtKB
- dTTP diphosphatase activity Source: UniProtKB-EC
- exonuclease activity Source: UniProtKB
- insulin receptor binding Source: BHF-UCL
- NADH pyrophosphatase activity Source: UniProtKB-EC
- nucleic acid binding Source: InterPro
- nucleoside-triphosphate diphosphatase activity Source: UniProtKB
- nucleotide diphosphatase activity Source: BHF-UCL
- phosphodiesterase I activity Source: UniProtKB
- polysaccharide binding Source: InterPro
- protein homodimerization activity Source: UniProtKB
- scavenger receptor activity Source: InterPro
- zinc ion binding Source: UniProtKB
GO - Biological processi
- 3'-phosphoadenosine 5'-phosphosulfate metabolic process Source: BHF-UCL
- ATP metabolic process Source: UniProtKB
- biomineral tissue development Source: UniProtKB-KW
- cellular phosphate ion homeostasis Source: BHF-UCL
- cellular response to insulin stimulus Source: BHF-UCL
- generation of precursor metabolites and energy Source: BHF-UCL
- immune response Source: InterPro
- inorganic diphosphate transport Source: BHF-UCL
- melanocyte differentiation Source: UniProtKB
- negative regulation of bone mineralization Source: UniProtKB
- negative regulation of cell growth Source: BHF-UCL
- negative regulation of fat cell differentiation Source: BHF-UCL
- negative regulation of glucose import Source: BHF-UCL
- negative regulation of glycogen biosynthetic process Source: BHF-UCL
- negative regulation of hh target transcription factor activity Source: UniProtKB
- negative regulation of insulin receptor signaling pathway Source: BHF-UCL
- negative regulation of protein autophosphorylation Source: BHF-UCL
- nucleic acid phosphodiester bond hydrolysis Source: UniProtKB
- nucleoside triphosphate catabolic process Source: BHF-UCL
- phosphate-containing compound metabolic process Source: BHF-UCL
- regulation of bone mineralization Source: GO_Central
- riboflavin metabolic process Source: Reactome
- sequestering of triglyceride Source: BHF-UCL
Keywordsi
Molecular function | Hydrolase |
Biological process | Biomineralization |
Ligand | Calcium, Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.6.1.9, 2681 |
PathwayCommonsi | P22413 |
Reactomei | R-HSA-196843, Vitamin B2 (riboflavin) metabolism R-HSA-199220, Vitamin B5 (pantothenate) metabolism |
SABIO-RKi | P22413 |
SIGNORi | P22413 |
Names & Taxonomyi
Protein namesi | Recommended name: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1Short name: E-NPP 11 Publication Alternative name(s): Membrane component chromosome 6 surface marker 1 Phosphodiesterase I/nucleotide pyrophosphatase 1 Plasma-cell membrane glycoprotein PC-11 Publication Cleaved into the following chain: Including the following 2 domains: |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3356, ENPP1 |
MIMi | 173335, gene |
neXtProti | NX_P22413 |
VEuPathDBi | HostDB:ENSG00000197594.11 |
Subcellular locationi
Plasma membrane
- Cell membrane 3 Publications; Single-pass type II membrane protein
- Basolateral cell membrane 1 Publication; Single-pass type II membrane protein
Note: Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts (PubMed:11598187). In bile duct cells and cancer cells, located to the apical cytoplasmic side (PubMed:11598187).1 Publication
Extracellular region or secreted
- Secreted By similarity
Note: Secreted following proteolytic cleavage.By similarity
Extracellular region or secreted
- extracellular space Source: BHF-UCL
Lysosome
- lysosomal membrane Source: UniProtKB
Plasma Membrane
- basolateral plasma membrane Source: BHF-UCL
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cell surface Source: BHF-UCL
- integral component of membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 76 | CytoplasmicSequence analysisAdd BLAST | 76 | |
Transmembranei | 77 – 97 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 98 – 925 | ExtracellularSequence analysisAdd BLAST | 828 |
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Ossification of the posterior longitudinal ligament of the spine (OPLL)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Patients with OPLL frequently present with a severe myelopathy that can lead to tetraparesis.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014141 | 91 | L → P in OPLL. 1 Publication | 1 | |
Natural variantiVAR_014143 | 287 | S → F in OPLL. 1 PublicationCorresponds to variant dbSNP:rs190947144EnsemblClinVar. | 1 |
Arterial calcification of infancy, generalized, 1 (GACI1)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077256 | 126 | C → R in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077259 | 195 | C → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs763457176Ensembl. | 1 | |
Natural variantiVAR_077260 | 195 | C → S in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication | 1 | |
Natural variantiVAR_077261 | 216 | S → Y in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs760786509Ensembl. | 1 | |
Natural variantiVAR_077262 | 218 | D → V in GACI1. 1 PublicationCorresponds to variant dbSNP:rs1231182870Ensembl. | 1 | |
Natural variantiVAR_077264 | 242 | G → E in GACI1; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_067910 | 250 | P → L in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs754659608Ensembl. | 1 | |
Natural variantiVAR_067911 | 252 | Missing in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077265 | 276 | D → N in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs143771474Ensembl. | 1 | |
Natural variantiVAR_077266 | 301 | Y → C in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication | 1 | |
Natural variantiVAR_067912 | 305 | P → T in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 3 PublicationsCorresponds to variant dbSNP:rs374270497EnsemblClinVar. | 1 | |
Natural variantiVAR_037433 | 342 | G → V in GACI1. 3 PublicationsCorresponds to variant dbSNP:rs121918025EnsemblClinVar. | 1 | |
Natural variantiVAR_077267 | 349 | R → K in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs764735802Ensembl. | 1 | |
Natural variantiVAR_037434 | 371 | Y → F in GACI1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs121918026EnsemblClinVar. | 1 | |
Natural variantiVAR_077268 | 456 | R → Q in GACI1. 1 PublicationCorresponds to variant dbSNP:rs765071179Ensembl. | 1 | |
Natural variantiVAR_077269 | 471 | Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs148462924Ensembl. | 1 | |
Natural variantiVAR_077270 | 481 | R → W in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs373044722EnsemblClinVar. | 1 | |
Natural variantiVAR_077271 | 500 | H → P in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077272 | 504 | S → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 Publications | 1 | |
Natural variantiVAR_077273 | 513 | Y → C in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs1243920034Ensembl. | 1 | |
Natural variantiVAR_067913 | 538 | D → H in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs387906673EnsemblClinVar. | 1 | |
Natural variantiVAR_077274 | 570 | Y → C in GACI1. 1 PublicationCorresponds to variant dbSNP:rs140248167Ensembl. | 1 | |
Natural variantiVAR_018514 | 579 | L → F in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs121918024EnsemblClinVar. | 1 | |
Natural variantiVAR_067914 | 586 | G → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs777367269EnsemblClinVar. | 1 | |
Natural variantiVAR_077276 | 659 | Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs143393727Ensembl. | 1 | |
Natural variantiVAR_077278 | 726 | C → R in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077279 | 777 | H → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs147346173EnsemblClinVar. | 1 | |
Natural variantiVAR_077280 | 792 | N → S in ARHR2 and GACI1. 2 PublicationsCorresponds to variant dbSNP:rs370184526Ensembl. | 1 | |
Natural variantiVAR_077281 | 804 | D → H in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077283 | 888 | R → W in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs184483616Ensembl. | 1 |
Diabetes mellitus, non-insulin-dependent (NIDDM)2 Publications
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Related information in OMIMHypophosphatemic rickets, autosomal recessive, 2 (ARHR2)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077255 | 92 | G → D in ARHR2. 1 Publication | 1 | |
Natural variantiVAR_077263 | 219 | G → R in ARHR2; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_063719 | 266 | G → V in ARHR2. 1 PublicationCorresponds to variant dbSNP:rs121908248EnsemblClinVar. | 1 | |
Natural variantiVAR_077280 | 792 | N → S in ARHR2 and GACI1. 2 PublicationsCorresponds to variant dbSNP:rs370184526Ensembl. | 1 | |
Natural variantiVAR_063720 | 901 | Y → S in ARHR2; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121908249EnsemblClinVar. | 1 |
Cole disease (COLED)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081644 | 120 | C → R in COLED; impaired homodimerization. 1 Publication | 1 | |
Natural variantiVAR_077257 | 133 | C → R in COLED; impaired homodimerization. 2 Publications | 1 | |
Natural variantiVAR_070782 | 149 | C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518477EnsemblClinVar. | 1 | |
Natural variantiVAR_070783 | 164 | C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518476EnsemblClinVar. | 1 | |
Natural variantiVAR_077258 | 177 | C → S in COLED. 1 Publication | 1 | |
Natural variantiVAR_070784 | 177 | C → Y in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518475EnsemblClinVar. | 1 |
Keywords - Diseasei
Diabetes mellitus, Disease variant, ObesityOrganism-specific databases
DisGeNETi | 5167 |
GeneReviewsi | ENPP1 |
MalaCardsi | ENPP1 |
MIMi | 125853, phenotype 208000, phenotype 602475, phenotype 613312, phenotype 615522, phenotype |
OpenTargetsi | ENSG00000197594 |
Orphaneti | 289176, Autosomal recessive hypophosphatemic rickets 51608, Generalized arterial calcification of infancy 324561, Hypopigmentation-punctate palmoplantar keratoderma syndrome 758, Pseudoxanthoma elasticum |
PharmGKBi | PA27791 |
Miscellaneous databases
Pharosi | P22413, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5925 |
DrugBanki | DB13893, Crotalus adamanteus antivenin DB11077, Polyethylene glycol 400 DB06408, Taribavirin |
DrugCentrali | P22413 |
Genetic variation databases
BioMutai | ENPP1 |
DMDMi | 23503088 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000188564 | 1 – 925 | Ectonucleotide pyrophosphatase/phosphodiesterase family member 1Add BLAST | 925 | |
ChainiPRO_0000447133 | 103 – 925 | Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted formBy similarityAdd BLAST | 823 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 108 ↔ 122 | PROSITE-ProRule annotation | ||
Disulfide bondi | 112 ↔ 140 | PROSITE-ProRule annotation | ||
Disulfide bondi | 120 ↔ 133 | PROSITE-ProRule annotation | ||
Disulfide bondi | 126 ↔ 132 | PROSITE-ProRule annotation | ||
Disulfide bondi | 149 ↔ 166 | PROSITE-ProRule annotation | ||
Disulfide bondi | 154 ↔ 184 | PROSITE-ProRule annotation | ||
Disulfide bondi | 164 ↔ 177 | PROSITE-ProRule annotation | ||
Disulfide bondi | 170 ↔ 176 | PROSITE-ProRule annotation | ||
Glycosylationi | 179 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 195 ↔ 241 | PROSITE-ProRule annotation | ||
Disulfide bondi | 203 ↔ 415 | PROSITE-ProRule annotation | ||
Modified residuei | 256 | PhosphothreonineBy similarity | 1 | |
Glycosylationi | 285 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 341 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 431 ↔ 530 | PROSITE-ProRule annotation | ||
Glycosylationi | 477 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 480 ↔ 868 | PROSITE-ProRule annotation | ||
Glycosylationi | 585 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 614 ↔ 672 | PROSITE-ProRule annotation | ||
Disulfide bondi | 626 ↔ 726 | PROSITE-ProRule annotation | ||
Disulfide bondi | 628 ↔ 711 | PROSITE-ProRule annotation | ||
Glycosylationi | 643 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 700 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 731 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 748 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 838 ↔ 848 | PROSITE-ProRule annotation |
Post-translational modificationi
Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity.1 Publication
N-glycosylated.3 Publications
The secreted form is produced through cleavage at Lys-103 by intracellular processing.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 102 – 103 | CleavageBy similarity | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
EPDi | P22413 |
jPOSTi | P22413 |
MassIVEi | P22413 |
MaxQBi | P22413 |
PaxDbi | P22413 |
PeptideAtlasi | P22413 |
PRIDEi | P22413 |
ProteomicsDBi | 53988 |
PTM databases
GlyConnecti | 1196, 19 N-Linked glycans (2 sites) |
GlyGeni | P22413, 9 sites |
iPTMneti | P22413 |
PhosphoSitePlusi | P22413 |
Expressioni
Tissue specificityi
Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis (PubMed:9344668). Expressed in melanocytes but not in keratinocytes (PubMed:28964717).2 Publications
Gene expression databases
Bgeei | ENSG00000197594, Expressed in tibia and 210 other tissues |
ExpressionAtlasi | P22413, baseline and differential |
Genevisiblei | P22413, HS |
Organism-specific databases
HPAi | ENSG00000197594, Low tissue specificity |
Interactioni
Subunit structurei
Monomeric (By similarity).
By similarityGO - Molecular functioni
- insulin receptor binding Source: BHF-UCL
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 111193, 21 interactors |
IntActi | P22413, 13 interactors |
MINTi | P22413 |
STRINGi | 9606.ENSP00000354238 |
Chemistry databases
BindingDBi | P22413 |
Miscellaneous databases
RNActi | P22413, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P22413 |
SMRi | P22413 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P22413 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 104 – 144 | SMB 1PROSITE-ProRule annotationAdd BLAST | 41 | |
Domaini | 145 – 189 | SMB 2PROSITE-ProRule annotationAdd BLAST | 45 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 191 – 591 | PhosphodiesteraseBy similarityAdd BLAST | 401 | |
Regioni | 597 – 647 | LinkerBy similarityAdd BLAST | 51 | |
Regioni | 654 – 925 | NucleaseBy similarityAdd BLAST | 272 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 45 – 52 | Di-leucine motifBy similarity | 8 |
Domaini
The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells.By similarity
Sequence similaritiesi
Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.Curated
Keywords - Domaini
Repeat, Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2645, Eukaryota |
GeneTreei | ENSGT00940000156034 |
HOGENOMi | CLU_012256_0_1_1 |
InParanoidi | P22413 |
OMAi | DHTESCA |
OrthoDBi | 999163at2759 |
PhylomeDBi | P22413 |
TreeFami | TF330032 |
Family and domain databases
Gene3Di | 3.40.720.10, 1 hit |
InterProi | View protein in InterPro IPR017850, Alkaline_phosphatase_core_sf IPR001604, DNA/RNA_non-sp_Endonuclease IPR029890, ENPP1 IPR020821, Extracellular_endonuc_su_A IPR002591, Phosphodiest/P_Trfase IPR036024, Somatomedin_B-like_dom_sf IPR020436, Somatomedin_B_chordata IPR001212, Somatomedin_B_dom |
PANTHERi | PTHR10151:SF77, PTHR10151:SF77, 1 hit |
Pfami | View protein in Pfam PF01223, Endonuclease_NS, 1 hit PF01663, Phosphodiest, 1 hit PF01033, Somatomedin_B, 2 hits |
PRINTSi | PR00022, SOMATOMEDINB |
SMARTi | View protein in SMART SM00892, Endonuclease_NS, 1 hit SM00477, NUC, 1 hit SM00201, SO, 2 hits |
SUPFAMi | SSF53649, SSF53649, 1 hit SSF90188, SSF90188, 2 hits |
PROSITEi | View protein in PROSITE PS00524, SMB_1, 2 hits PS50958, SMB_2, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
P22413-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MERDGCAGGG SRGGEGGRAP REGPAGNGRD RGRSHAAEAP GDPQAAASLL
60 70 80 90 100
APMDVGEEPL EKAARARTAK DPNTYKVLSL VLSVCVLTTI LGCIFGLKPS
110 120 130 140 150
CAKEVKSCKG RCFERTFGNC RCDAACVELG NCCLDYQETC IEPEHIWTCN
160 170 180 190 200
KFRCGEKRLT RSLCACSDDC KDKGDCCINY SSVCQGEKSW VEEPCESINE
210 220 230 240 250
PQCPAGFETP PTLLFSLDGF RAEYLHTWGG LLPVISKLKK CGTYTKNMRP
260 270 280 290 300
VYPTKTFPNH YSIVTGLYPE SHGIIDNKMY DPKMNASFSL KSKEKFNPEW
310 320 330 340 350
YKGEPIWVTA KYQGLKSGTF FWPGSDVEIN GIFPDIYKMY NGSVPFEERI
360 370 380 390 400
LAVLQWLQLP KDERPHFYTL YLEEPDSSGH SYGPVSSEVI KALQRVDGMV
410 420 430 440 450
GMLMDGLKEL NLHRCLNLIL ISDHGMEQGS CKKYIYLNKY LGDVKNIKVI
460 470 480 490 500
YGPAARLRPS DVPDKYYSFN YEGIARNLSC REPNQHFKPY LKHFLPKRLH
510 520 530 540 550
FAKSDRIEPL TFYLDPQWQL ALNPSERKYC GSGFHGSDNV FSNMQALFVG
560 570 580 590 600
YGPGFKHGIE ADTFENIEVY NLMCDLLNLT PAPNNGTHGS LNHLLKNPVY
610 620 630 640 650
TPKHPKEVHP LVQCPFTRNP RDNLGCSCNP SILPIEDFQT QFNLTVAEEK
660 670 680 690 700
IIKHETLPYG RPRVLQKENT ICLLSQHQFM SGYSQDILMP LWTSYTVDRN
710 720 730 740 750
DSFSTEDFSN CLYQDFRIPL SPVHKCSFYK NNTKVSYGFL SPPQLNKNSS
760 770 780 790 800
GIYSEALLTT NIVPMYQSFQ VIWRYFHDTL LRKYAEERNG VNVVSGPVFD
810 820 830 840 850
FDYDGRCDSL ENLRQKRRVI RNQEILIPTH FFIVLTSCKD TSQTPLHCEN
860 870 880 890 900
LDTLAFILPH RTDNSESCVH GKHDSSWVEE LLMLHRARIT DVEHITGLSF
910 920
YQQRKEPVSD ILKLKTHLPT FSQED
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PE72 | E9PE72_HUMAN | Ectonucleotide pyrophosphatase/phos... | ENPP1 | 378 | Annotation score: | ||
A0A3B3IST7 | A0A3B3IST7_HUMAN | Ectonucleotide pyrophosphatase/phos... | ENPP1 | 56 | Annotation score: | ||
A0A3B3ISN7 | A0A3B3ISN7_HUMAN | Ectonucleotide pyrophosphatase/phos... | ENPP1 | 110 | Annotation score: | ||
A0A3B3IU14 | A0A3B3IU14_HUMAN | Ectonucleotide pyrophosphatase/phos... | ENPP1 | 68 | Annotation score: |
Sequence cautioni
The sequence AAA63237 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAH59375 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAA02054 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014141 | 91 | L → P in OPLL. 1 Publication | 1 | |
Natural variantiVAR_077255 | 92 | G → D in ARHR2. 1 Publication | 1 | |
Natural variantiVAR_081644 | 120 | C → R in COLED; impaired homodimerization. 1 Publication | 1 | |
Natural variantiVAR_077256 | 126 | C → R in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077257 | 133 | C → R in COLED; impaired homodimerization. 2 Publications | 1 | |
Natural variantiVAR_070782 | 149 | C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518477EnsemblClinVar. | 1 | |
Natural variantiVAR_070783 | 164 | C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518476EnsemblClinVar. | 1 | |
Natural variantiVAR_008873 | 173 | K → Q Associated with NIDDM; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 6 PublicationsCorresponds to variant dbSNP:rs1044498EnsemblClinVar. | 1 | |
Natural variantiVAR_077258 | 177 | C → S in COLED. 1 Publication | 1 | |
Natural variantiVAR_070784 | 177 | C → Y in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518475EnsemblClinVar. | 1 | |
Natural variantiVAR_037432 | 179 | N → S. Corresponds to variant dbSNP:rs2273411Ensembl. | 1 | |
Natural variantiVAR_077259 | 195 | C → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs763457176Ensembl. | 1 | |
Natural variantiVAR_077260 | 195 | C → S in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication | 1 | |
Natural variantiVAR_077261 | 216 | S → Y in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs760786509Ensembl. | 1 | |
Natural variantiVAR_077262 | 218 | D → V in GACI1. 1 PublicationCorresponds to variant dbSNP:rs1231182870Ensembl. | 1 | |
Natural variantiVAR_077263 | 219 | G → R in ARHR2; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_077264 | 242 | G → E in GACI1; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_067910 | 250 | P → L in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs754659608Ensembl. | 1 | |
Natural variantiVAR_067911 | 252 | Missing in GACI1. 1 Publication | 1 | |
Natural variantiVAR_063719 | 266 | G → V in ARHR2. 1 PublicationCorresponds to variant dbSNP:rs121908248EnsemblClinVar. | 1 | |
Natural variantiVAR_014142 | 268 | Y → H1 PublicationCorresponds to variant dbSNP:rs17847050EnsemblClinVar. | 1 | |
Natural variantiVAR_077265 | 276 | D → N in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs143771474Ensembl. | 1 | |
Natural variantiVAR_014143 | 287 | S → F in OPLL. 1 PublicationCorresponds to variant dbSNP:rs190947144EnsemblClinVar. | 1 | |
Natural variantiVAR_077266 | 301 | Y → C in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication | 1 | |
Natural variantiVAR_067912 | 305 | P → T in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 3 PublicationsCorresponds to variant dbSNP:rs374270497EnsemblClinVar. | 1 | |
Natural variantiVAR_037433 | 342 | G → V in GACI1. 3 PublicationsCorresponds to variant dbSNP:rs121918025EnsemblClinVar. | 1 | |
Natural variantiVAR_077267 | 349 | R → K in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs764735802Ensembl. | 1 | |
Natural variantiVAR_037434 | 371 | Y → F in GACI1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs121918026EnsemblClinVar. | 1 | |
Natural variantiVAR_077268 | 456 | R → Q in GACI1. 1 PublicationCorresponds to variant dbSNP:rs765071179Ensembl. | 1 | |
Natural variantiVAR_077269 | 471 | Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs148462924Ensembl. | 1 | |
Natural variantiVAR_077270 | 481 | R → W in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs373044722EnsemblClinVar. | 1 | |
Natural variantiVAR_077271 | 500 | H → P in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077272 | 504 | S → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 Publications | 1 | |
Natural variantiVAR_077273 | 513 | Y → C in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs1243920034Ensembl. | 1 | |
Natural variantiVAR_067913 | 538 | D → H in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs387906673EnsemblClinVar. | 1 | |
Natural variantiVAR_077274 | 570 | Y → C in GACI1. 1 PublicationCorresponds to variant dbSNP:rs140248167Ensembl. | 1 | |
Natural variantiVAR_018514 | 579 | L → F in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs121918024EnsemblClinVar. | 1 | |
Natural variantiVAR_067914 | 586 | G → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs777367269EnsemblClinVar. | 1 | |
Natural variantiVAR_077275 | 611 | L → V1 PublicationCorresponds to variant dbSNP:rs79079368EnsemblClinVar. | 1 | |
Natural variantiVAR_077276 | 659 | Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs143393727Ensembl. | 1 | |
Natural variantiVAR_077277 | 668 | E → K No effect on nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs115371819EnsemblClinVar. | 1 | |
Natural variantiVAR_077278 | 726 | C → R in GACI1. 1 Publication | 1 | |
Natural variantiVAR_018515 | 774 | R → C Decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 4 PublicationsCorresponds to variant dbSNP:rs28933977EnsemblClinVar. | 1 | |
Natural variantiVAR_077279 | 777 | H → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs147346173EnsemblClinVar. | 1 | |
Natural variantiVAR_014144 | 779 | T → P1 PublicationCorresponds to variant dbSNP:rs1805138EnsemblClinVar. | 1 | |
Natural variantiVAR_077280 | 792 | N → S in ARHR2 and GACI1. 2 PublicationsCorresponds to variant dbSNP:rs370184526Ensembl. | 1 | |
Natural variantiVAR_077281 | 804 | D → H in GACI1. 1 Publication | 1 | |
Natural variantiVAR_077282 | 821 | R → H Decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs367759638EnsemblClinVar. | 1 | |
Natural variantiVAR_037435 | 886 | R → T. Corresponds to variant dbSNP:rs8192683EnsemblClinVar. | 1 | |
Natural variantiVAR_077283 | 888 | R → W in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs184483616Ensembl. | 1 | |
Natural variantiVAR_063720 | 901 | Y → S in ARHR2; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121908249EnsemblClinVar. | 1 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000647893; ENSP00000498074; ENSG00000197594 |
GeneIDi | 5167 |
KEGGi | hsa:5167 |
UCSCi | uc011ecf.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2YS0 | NMR | - | A | 147-189 | [»] | |
6WET | X-ray | 2.60 | AaA/BaB | 1-925 | [»] | |
6WEU | X-ray | 2.65 | AbA/BbB | 1-925 | [»] | |
6WEV | X-ray | 2.90 | AbA/BbB | 1-925 | [»] | |
6WEW | X-ray | 2.73 | AbA/BaB | 1-925 | [»] | |
6WFJ | X-ray | 2.50 | AcA/BcB | 1-925 | [»] | |
BMRBi | P22413 | |||||
SMRi | P22413 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111193, 21 interactors |
IntActi | P22413, 13 interactors |
MINTi | P22413 |
STRINGi | 9606.ENSP00000354238 |
Chemistry databases
BindingDBi | P22413 |
ChEMBLi | CHEMBL5925 |
DrugBanki | DB13893, Crotalus adamanteus antivenin DB11077, Polyethylene glycol 400 DB06408, Taribavirin |
DrugCentrali | P22413 |
PTM databases
GlyConnecti | 1196, 19 N-Linked glycans (2 sites) |
GlyGeni | P22413, 9 sites |
iPTMneti | P22413 |
PhosphoSitePlusi | P22413 |
Genetic variation databases
BioMutai | ENPP1 |
DMDMi | 23503088 |
Proteomic databases
EPDi | P22413 |
jPOSTi | P22413 |
MassIVEi | P22413 |
MaxQBi | P22413 |
PaxDbi | P22413 |
PeptideAtlasi | P22413 |
PRIDEi | P22413 |
ProteomicsDBi | 53988 |
Protocols and materials databases
Antibodypediai | 32916, 404 antibodies |
Genome annotation databases
Ensembli | ENST00000647893; ENSP00000498074; ENSG00000197594 |
GeneIDi | 5167 |
KEGGi | hsa:5167 |
UCSCi | uc011ecf.2, human |
Organism-specific databases
CTDi | 5167 |
DisGeNETi | 5167 |
GeneCardsi | ENPP1 |
GeneReviewsi | ENPP1 |
HGNCi | HGNC:3356, ENPP1 |
HPAi | ENSG00000197594, Low tissue specificity |
MalaCardsi | ENPP1 |
MIMi | 125853, phenotype 173335, gene 208000, phenotype 602475, phenotype 613312, phenotype 615522, phenotype |
neXtProti | NX_P22413 |
OpenTargetsi | ENSG00000197594 |
Orphaneti | 289176, Autosomal recessive hypophosphatemic rickets 51608, Generalized arterial calcification of infancy 324561, Hypopigmentation-punctate palmoplantar keratoderma syndrome 758, Pseudoxanthoma elasticum |
PharmGKBi | PA27791 |
VEuPathDBi | HostDB:ENSG00000197594.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2645, Eukaryota |
GeneTreei | ENSGT00940000156034 |
HOGENOMi | CLU_012256_0_1_1 |
InParanoidi | P22413 |
OMAi | DHTESCA |
OrthoDBi | 999163at2759 |
PhylomeDBi | P22413 |
TreeFami | TF330032 |
Enzyme and pathway databases
BRENDAi | 3.6.1.9, 2681 |
PathwayCommonsi | P22413 |
Reactomei | R-HSA-196843, Vitamin B2 (riboflavin) metabolism R-HSA-199220, Vitamin B5 (pantothenate) metabolism |
SABIO-RKi | P22413 |
SIGNORi | P22413 |
Miscellaneous databases
BioGRID-ORCSi | 5167, 5 hits in 990 CRISPR screens |
ChiTaRSi | ENPP1, human |
EvolutionaryTracei | P22413 |
GeneWikii | Ectonucleotide_pyrophosphatase/phosphodiesterase_1 |
GenomeRNAii | 5167 |
Pharosi | P22413, Tchem |
PROi | PR:P22413 |
RNActi | P22413, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000197594, Expressed in tibia and 210 other tissues |
ExpressionAtlasi | P22413, baseline and differential |
Genevisiblei | P22413, HS |
Family and domain databases
Gene3Di | 3.40.720.10, 1 hit |
InterProi | View protein in InterPro IPR017850, Alkaline_phosphatase_core_sf IPR001604, DNA/RNA_non-sp_Endonuclease IPR029890, ENPP1 IPR020821, Extracellular_endonuc_su_A IPR002591, Phosphodiest/P_Trfase IPR036024, Somatomedin_B-like_dom_sf IPR020436, Somatomedin_B_chordata IPR001212, Somatomedin_B_dom |
PANTHERi | PTHR10151:SF77, PTHR10151:SF77, 1 hit |
Pfami | View protein in Pfam PF01223, Endonuclease_NS, 1 hit PF01663, Phosphodiest, 1 hit PF01033, Somatomedin_B, 2 hits |
PRINTSi | PR00022, SOMATOMEDINB |
SMARTi | View protein in SMART SM00892, Endonuclease_NS, 1 hit SM00477, NUC, 1 hit SM00201, SO, 2 hits |
SUPFAMi | SSF53649, SSF53649, 1 hit SSF90188, SSF90188, 2 hits |
PROSITEi | View protein in PROSITE PS00524, SMB_1, 2 hits PS50958, SMB_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ENPP1_HUMAN | |
Accessioni | P22413Primary (citable) accession number: P22413 Secondary accession number(s): Q5T9R6 Q9Y6K3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1991 |
Last sequence update: | September 19, 2002 | |
Last modified: | April 7, 2021 | |
This is version 219 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families