Protein detail
SL9A1
Sodium/hydrogen exchanger 1 (APNH) (Na(+)/H(+) antiporter, amiloride-sensitive) (Na(+)/H(+) exchanger 1) (NHE-1) (Solute carrier family 9 member 1)
Protein symbol SL9A1 | UniProt ID | EVMP score 0.63 |
Frequency 6 | Transmembrane count 13 | Protein classification Disease related genesHuman disease related genesMetabolic proteinsPotential drug targetsPredicted membrane proteinsTransporters |
Basic Information
Protein Names
Sodium/hydrogen exchanger 1 (APNH) (Na(+)/H(+) antiporter, amiloride-sensitive) (Na(+)/H(+) exchanger 1) (NHE-1) (Solute carrier family 9 member 1)
Protein Class
Disease related genesHuman disease related genesMetabolic proteinsPotential drug targetsPredicted membrane proteinsTransporters
Protein Function
- Human disease related genes:Nervous system diseases:Neurodegenerative diseases
- Disease related genes
- Transporters:Electrochemical Potential-driven transporters
- Potential drug targets
Transmembrane
99..121; Helical; Name=1; 131..148; Helical; Name=2; 159..176; Helical; Name=3; 187..215; Helical; Name=4; 223..249; Helical; Name=5; 253..283; Helical; Name=6; 288..322; Helical; Name=7; 329..341; Helical; Name=8; 351..371; Helical; Name=9; 374..404; Helical; Name=10; 411..438; Helical; Name=11; 445..469; Helical; Name=12; 476..505; Helical; Name=13
Transmembrane Count
13
Ensembl
Entrez Gene Symbol
Gene Synonym
APNHNHE-1NHE1PPP1R143
Gene Description
Solute carrier family 9 member A1
Chromosome
1
Position
27098809-27166981
Frequency
6
EVMP Score
0.63
Fluorescence & Localization
Cell SpecificEndometrial glandular cells
Function & Pathway
Protein Function
- Human disease related genes:Nervous system diseases:Neurodegenerative diseases
- Disease related genes
- Transporters:Electrochemical Potential-driven transporters
- Potential drug targets
Cellular Component
- GO:0005654 nucleoplasm
- GO:0005737 cytoplasm
- GO:0005739 mitochondrion
- GO:0005886 plasma membrane
- GO:0005925 focal adhesion
- GO:0009986 cell surface
- GO:0014704 intercalated disc
- GO:0016020 membrane
- GO:0016323 basolateral plasma membrane
- GO:0016324 apical plasma membrane
- GO:0030027 lamellipodium
- GO:0030315 T-tubule
- GO:0045121 membrane raft
- GO:0048471 perinuclear region of cytoplasm
- GO:0070062 extracellular exosome
- GO:0090533 cation-transporting ATPase complex
Molecular Function
- GO:0005515 protein binding
- GO:0005516 calmodulin binding
- GO:0005543 phospholipid binding
- GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
- GO:0015385 sodium:proton antiporter activity
- GO:0015386 potassium:proton antiporter activity
- GO:0030346 protein phosphatase 2B binding
- GO:0030674 protein-macromolecule adaptor activity
- GO:0042802 identical protein binding
- GO:0048306 calcium-dependent protein binding
- GO:0060090 molecular adaptor activity
Biological Process
KEGG
- hsa04024 cAMP signaling pathway
- KEGG:hsa04260 Cardiac muscle contraction
- KEGG:hsa04261 Adrenergic signaling in cardiomyocytes
- KEGG:hsa04371 Apelin signaling pathway
- KEGG:hsa04810 Regulation of actin cytoskeleton
- KEGG:hsa04919 Thyroid hormone signaling pathway
- KEGG:hsa04970 Salivary secretion
- KEGG:hsa04971 Gastric acid secretion
- KEGG:hsa04972 Pancreatic secretion
- KEGG:hsa04976 Bile secretion
- KEGG:hsa05205 Proteoglycans in cancer
Reactome
- R-hsa-1630316 glycosaminoglycan metabolism
- R-hsa-2160916 hyaluronan degradation
- R-hsa-2142845 hyaluronan metabolism
- R-hsa-71387 metabolism of carbohydrates and carbohydrate derivatives
- R-hsa-425410 metal ion slc transporters
- R-hsa-425407 slc mediated transmembrane transport
- R-hsa-425986 sodium proton exchangers
- R-hsa-382551 transport of small molecules
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
45 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| SLC9A1 | SGK1 | O00141 | S | 703 | phosphorylation | RLIMS-P_ProtMapperREACH_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:25270604ProtMapper:27517916 |
| SLC9A1 | CANX | P27824 | S | 703 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:10400637 |
| SLC9A1 | MAP4K4 | O95819 | S | 648 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:22216214 |
| SLC9A1 | INS | P01308 | S | 648 | phosphorylation | REACH_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:25578862 |
| SLC9A1 | MAPK11 | Q15759 | S | 726 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:9776729ProtMapper:11604491 |
| SLC9A1 | MAPK11 | Q15759 | S | 723 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:9776729ProtMapper:11604491 |
| SLC9A1 | MAPK11 | Q15759 | T | 718 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:9776729ProtMapper:11604491 |
| SLC9A1 | MAPK11 | Q15759 | S | 729 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:9776729ProtMapper:11604491 |
| SLC9A1 | GH1 | P01241 | S | 703 | phosphorylation | Sparser_ProtMapperProtMapper | |
| SLC9A1 | CDK1 | P06493 | S | 726 | phosphorylation | KEA | KEA:17570479 |
Ligand-Receptor Signaling
29 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | Yes | No |
| basolateral_cell_membrane | plasma_membrane | UniProt_location | No | No | No | Yes | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | Yes | No |
| plasma_membrane_transmembrane | plasma_membrane_transmembrane | CSPA | No | No | No | Yes | No |
| plasma_membrane_transmembrane | plasma_membrane_transmembrane | OmniPath | No | No | No | Yes | No |
| cell_surface | cell_surface | Surfaceome | No | No | No | Yes | No |
| cell_surface | cell_surface | OmniPath | No | No | No | Yes | No |
| receptor | receptor | scConnect | No | Yes | No | Yes | No |
| transmembrane | transmembrane_predicted | Phobius | No | No | No | Yes | No |
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Regulatory Interaction Network
7 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| MK01 | P28482 | SL9A1 | P19634 | Yes | Yes | No | HPRD_MIMPSIGNORProtMapperPhosphoSite_KEAHPRDPhosphoSite_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoSite_norefPhosphoPointiPTMnetKEAHPRD_KEASIGNOR_ProtMapperREACH_ProtMapperPhosphoSiteAdhesomeHPRD-phos | HPRD-phos:19415658HPRD-phos:18088087ProtMapper:15253667HPRD-phos:18669648ProtMapper:19415658ProtMapper:18669648HPRD-phos:15253667PhosphoSite:23678047Adhesome:15253667PhosphoSite:23602949PhosphoSite:25162926SIGNOR:17209041HPRD-phos:20068231ProtMapper:18088087HPRD:15253667HPRD-phos:20058876PhosphoSite:11604491PhosphoSite:18701649PhosphoSite:28554535ProtMapper:20058876KEA:15253667ProtMapper:17209041PhosphoSite:15253667ProtMapper:20068231PhosphoSite:27049728ProtMapper:24745981 |
| MK14 | Q16539 | SL9A1 | P19634 | Yes | Yes | No | HPRD_MIMPSIGNORProtMapperPhosphoSite_KEAphosphoELM_KEAPhosphoNetworksNCI-PID_ProtMapperHPRDWangPhosphoSite_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoSite_norefPhosphoPointiPTMnetKEAHPRD_KEAphosphoELMSIGNOR_ProtMapperHPRD-phos | KEA:11604491HPRD:11604491HPRD-phos:11604491SIGNOR:11604491ProtMapper:20068231ProtMapper:9776729HPRD-phos:20068231HPRD-phos:18669648ProtMapper:18701649SIGNOR:18701649phosphoELM:11604491ProtMapper:18669648ProtMapper:11604491 |
| M3K14 | Q99558 | SL9A1 | P19634 | Yes | Yes | No | REACH_ProtMapperSIGNORProtMapper | ProtMapper:22216214SIGNOR:11369779 |
| ROCK1 | Q13464 | SL9A1 | P19634 | Yes | Yes | No | AdhesomeiPTMnetSIGNORProtMapperWangPhosphoSite_ProtMapper | SIGNOR:27302366Adhesome:10592173 |
| KS6A1 | Q15418 | SL9A1 | P19634 | Yes | Yes | No | Sparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperRLIMS-P_ProtMapperPhosphoSite_KEAKEASIGNOR_ProtMapperPhosphoSite_ProtMapper | ProtMapper:10400637ProtMapper:23431433KEA:10400637ProtMapper:27049728SIGNOR:10400637 |
| AKT1 | P31749 | SL9A1 | P19634 | Yes | Yes | No | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetProtMapperWangPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:20026127PhosphoSite:10400637PhosphoSite:18757828PhosphoSite:33655882PhosphoSite:16475831 |
| BRAF | P15056 | SL9A1 | P19634 | Yes | No | No | RLIMS-P_ProtMapperPhosphoSitePhosphoSite_ProtMapperProtMapper | PhosphoSite:25578862ProtMapper:27555478PhosphoSite:27555478 |
Protein Complex Composition
10 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| Sodium/proton exchanger complexNHE1-CHP1 variant | CHP1SLC9A1 | P19634Q99653 | 2:2 | ComplexPortalPDB | PDB:2e30PDB:2E30PDB:7DSVPDB:7dsvPDB:7DSXintact:EBI-61295944PDB:7dsx | 341084581475529217050540 |
| Sodium/proton exchanger complexNHE1-CHP2 variant | CHP2SLC9A1 | O43745P19634 | 2:2 | ComplexPortalPDB | intact:EBI-63179793PDB:2BECPDB:2bec | 167102971475529231912575 |
| Sodium/proton exchanger complexNHE1-CHP3 variant | SLC9A1TESC | P19634Q96BS2 | 2:2 | ComplexPortal | intact:EBI-63180706 | 147552923028785323506868 |
| CALM1SLC9A1 | P0DP23P19634 | 1:2 | PDB | PDB:6zbi | ||
| SLC9A1 | P19634 | 2 | PDB | PDB:7dsw | ||
| MAP2K2MAPK3SLC9A1 | P19634P27361P36507 | 1:1:1 | CompleatCFinder | Compleat:HC8610 | ||
| LPAR1MFSD5SLC9A1 | P19634Q6N075Q92633 | 0:0:0 | hu.MAP | |||
| EXTL2LPAR1MFSD5SLC9A1 | P19634Q6N075Q92633Q9UBQ6 | 0:0:0:0 | hu.MAP | |||
| GALNT7SLC9A1 | P19634Q86SF2 | 0:0 | hu.MAP2 | |||
| LPAR1SLC9A1 | P19634Q92633 | 0:0 | hu.MAP |
Sequence, Structure & Domains
Sequences
Length
815
Mass
90,763
Sequence
MVLRSGICGLSPHRIFPSLLVVVALVGLLPVLRSHGLQLSPTASTIRSSEPPRERSIGDVTTAPPEVTPESRPVNHSVTDHGMKPRKAFPVLGIDYTHVRTPFEISLWILLACLMKIGFHVIPTISSIVPESCLLIVVGLLVGGLIKGVGETPPFLQSDVFFLFLLPPIILDAGYFLPLRQFTENLGTILIFAVVGTLWNAFFLGGLMYAVCLVGGEQINNIGLLDNLLFGSIISAVDPVAVLAVFEEIHINELLHILVFGESLLNDAVTVVLYHLFEEFANYEHVGIVDIFLGFLSFFVVALGGVLVGVVYGVIAAFTSRFTSHIRVIEPLFVFLYSYMAYLSAELFHLSGIMALIASGVVMRPYVEANISHKSHTTIKYFLKMWSSVSETLIFIFLGVSTVAGSHHWNWTFVISTLLFCLIARVLGVLGLTWFINKFRIVKLTPKDQFIIAYGGLRGAIAFSLGYLLDKKHFPMCDLFLTAIITVIFFTVFVQGMTIRPLVDLLAVKKKQETKRSINEEIHTQFLDHLLTGIEDICGHYGHHHWKDKLNRFNKKYVKKCLIAGERSKEPQLIAFYHKMEMKQAIELVESGGMGKIPSAVSTVSMQNIHPKSLPSERILPALSKDKEEEIRKILRNNLQKTRQRLRSYNRHTLVADPYEEAWNQMLLRRQKARQLEQKINNYLTVPAHKLDSPTMSRARIGSDPLAYEPKEDLPVITIDPASPQSPESVDLVNEELKGKVLGLSRDPAKVAEEDEDDDGGIMMRSKETSSPGTDDVFTPAPSDSPSSQRIQRCLSDPGPHPEPGEGEPFFPKGQ
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P19634-1; Sequence=Displayed; Name=2; IsoId=P19634-2; Sequence=VSP_022101, VSP_022102
Alternative Sequence
496..554; GMTIRPLVDLLAVKKKQETKRSINEEIHTQFLDHLLTGIEDICGHYGHHHWKDKLNRFN -> VLGQGRAGPCLGDPHRLFPWKERKACDLKCDSSPSSTTNLLCDLGRATPPFWASVSSIVK (in isoform 2); 555..815; Missing (in isoform 2)
3D Structural Models
Turn
126..128; 180..182; 247..250; 437..439; 494..498; 682..684
Helix
101..120; 131..149; 160..164; 166..175; 183..185; 186..214; 225..234; 239..245; 253..280; 288..320; 327..329; 330..347; 352..366; 373..403; 411..436; 446..453; 462..467; 477..493; 500..504; 518..538; 544..557; 572..590; 625..651; 658..681
Beta Strand
89..91; 97..100; 217..221; 282..285; 367..371; 440..442; 471..473; 558..562; 716..720
3D Structure
Electron microscopy (3); NMR spectroscopy (8); X-ray crystallography (5)
Domain & Motif Annotations
Compositional Bias
782..791; Polar residues
Domain (CC)
The C-terminal intracellular domain is subject to extensive post-translational modifications and binding partner interactions which regulate transporter activity, scaffolding functions, downstream events and localization.
Region
42..79; Disordered; 503..545; Interaction with TESC; 509..516; PI(4,5)P2-binding region; 515..545; Interaction with CHP2; 540..545; Confers pH-dependent PI(4,5)P2 binding; 552..560; PI(4,5)P2-binding region; 633..815; Interaction with CALM1; 633..815; Interaction with TESC; 684..687; Interaction with PPP3CA; 715..720; Interaction with PPP3CA; 744..815; Disordered
Protein Families
Monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family
Sequence Similarities
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
Clinical Relevance
Disease Involvement
DeafnessDisease variantNeurodegeneration
Biomarker
Phase 3; Discontinued in Phase 2; Terminated; Investigative
Drug Targets
Literature-reported targetClinical trial targetSuccessful target
Interaction Protein
ENSG00000088992ENSG00000166869ENSG00000187446
Interaction Count
3
Interaction Dataset
intact_biogrid