Q148W0

SS
Gene name
Atp8b1
Protein name
Phospholipid-transporting ATPase IC
Names
EC 7.6.2.1 , ATPase class I type 8B member 1 , P4-ATPase flippase complex alpha subunit ATP8B1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:54670
EC number
7.6.2.1: Linked to the hydrolysis of a nucleoside triphosphate
Protein Class

Descriptions

ATP8B1 is a catalytic component of a P4-ATPase flippase complex which flips lipids from the exoplasmic to the cytosolic leaflet, thus maintaining lipid asymmetry in eukaryotic cell membranes. Mutations in ATP8B1 are associated with severe diseases, for example, causing progressive familial intrahepatic cholestasis, a rare inherited disorder progressing toward liver failure. ATP8B1 forms a binary complex with CDC50A and displays a broad specificity to glycerophospholipids. ATP8B1 is autoinhibited by its N- and C-terminal tails, which form extensive interactions with the catalytic sites and flexible domain interfaces. ATP hydrolysis is unleashed by truncation of the C-terminus, but also requires phosphoinositides, most markedly phosphatidylinositol-3,4,5-phosphate (PI(3,4,5)P3), and removal of both N- and C-termini results in full activation.

Autoinhibitory domains (AIDs)

1174-1251 (C-terminal tail) SS

Target domain

65-325 (A-domain);461-709 (N-domain);710-928 (P-domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q148W0

Entry ID Method Resolution Chain Position Source
AF-Q148W0-F1 Predicted AlphaFoldDB

45 variants for Q148W0

Variant ID(s) Position Change Description Diseaes Association Provenance
rs255597391 2 S>N No EVA
rs3389522235 17 P>H No EVA
rs3389516201 54 K>M No EVA
rs3389522274 159 D>N No EVA
rs3389486720 163 D>V No EVA
rs3389516149 174 N>T No EVA
rs3389507614 205 N>K No EVA
rs3412941765 229 A>V No EVA
rs3389464584 318 K>E No EVA
rs3389511628 356 A>V No EVA
rs3389464511 369 Y>N No EVA
rs3389519131 409 E>K No EVA
rs3407990376 412 R>P No EVA
rs3389511668 428 A>D No EVA
rs3389506603 458 T>I No EVA
rs3413084382 461 Q>L No EVA
rs3408668362 472 N>I No EVA
rs3389500246 489 K>T No EVA
rs36846647 508 Y>S No EVA
rs38397665 513 I>F No EVA
rs3389504251 547 N>T No EVA
rs3389508140 573 T>M No EVA
rs262174063 580 S>R No EVA
rs3389508144 593 I>S No EVA
rs3389519203 594 L>M No EVA
rs39711551 667 T>A No EVA
rs212421958 671 N>K No EVA
rs3389507619 682 N>I No EVA
rs3389500229 702 G>E No EVA
rs3389464566 715 P>L No EVA
rs3389473215 830 E>* No EVA
rs3389486712 833 R>G No EVA
rs3389507590 862 A>T No EVA
rs3412891463 862 A>V No EVA
rs3389504386 903 T>I No EVA
rs3389500797 909 G>E No EVA
rs3408840813 916 M>R No EVA
rs3408745360 932 L>Q No EVA
rs3389516212 940 G>S No EVA
rs1133955542 972 N>K No EVA
rs3389500272 1019 Y>* No EVA
rs3389456675 1020 V>G No EVA
rs3389500775 1089 G>V No EVA
rs3389473253 1133 T>I No EVA
rs3389508188 1207 S>L No EVA

No associated diseases with Q148W0

11 regional properties for Q148W0

Type Name Position InterPro Accession
domain FERM domain 35 - 355 IPR000299
domain Protein kinase domain 422 - 680 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 422 - 676 IPR001245
domain Focal adhesion kinase, targeting (FAT) domain 914 - 1045 IPR005189
active_site Tyrosine-protein kinase, active site 542 - 554 IPR008266
binding_site Protein kinase, ATP binding site 428 - 454 IPR017441
domain FERM central domain 135 - 250 IPR019748
domain Band 4.1 domain 31 - 258 IPR019749
domain Tyrosine-protein kinase, catalytic domain 422 - 676 IPR020635
domain Focal adhesion kinase, N-terminal 35 - 130 IPR041390
domain FAK1/PYK2, FERM domain C-lobe 254 - 364 IPR041784

Functions

Description
EC Number 7.6.2.1 Linked to the hydrolysis of a nucleoside triphosphate
Subcellular Localization
  • Cell membrane ; Multi-pass membrane protein
  • Apical cell membrane
  • Cell projection, stereocilium
  • Endoplasmic reticulum
  • Golgi apparatus
  • Exit from the endoplasmic reticulum requires the presence of TMEM30A or TMEM30B
  • Localizes to apical membranes in epithelial cells
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
apical plasma membrane The region of the plasma membrane located at the apical end of the cell.
brush border membrane The portion of the plasma membrane surrounding the brush border.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
nuclear body Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins.
phospholipid-translocating ATPase complex A protein complex that functions as a phospholipid-translocating P-Type ATPase.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
stereocilium An actin-based protrusion from the apical surface of auditory and vestibular hair cells and of neuromast cells. These protrusions are supported by a bundle of cross-linked actin filaments (an actin cable), oriented such that the plus (barbed) ends are at the tip of the protrusion, capped by a tip complex which bridges to the plasma. Bundles of stereocilia act as mechanosensory organelles.
trans-Golgi network The network of interconnected tubular and cisternal structures located within the Golgi apparatus on the side distal to the endoplasmic reticulum, from which secretory vesicles emerge. The trans-Golgi network is important in the later stages of protein secretion where it is thought to play a key role in the sorting and targeting of secreted proteins to the correct destination.

11 GO annotations of molecular function

Name Definition
aminophospholipid flippase activity Enables the transfer of aminophospholipids from the exoplasmic to the cytosolic leaftlet of a membrane, using energy from the hydrolysis of ATP. Aminophospholipids contain phosphoric acid as a mono- or diester and an amino (NH2) group.
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ATP hydrolysis activity Catalysis of the reaction
ATPase-coupled intramembrane lipid transporter activity Catalysis of the movement of lipids from one membrane leaflet to the other, driven by ATP hydrolysis. This includes flippases and floppases.
cardiolipin binding Binding to cardiolipin.
lipid transporter activity Enables the directed movement of lipids into, out of or within a cell, or between cells.
magnesium ion binding Binding to a magnesium (Mg) ion.
phosphatidylcholine flippase activity Catalysis of the movement of phosphatidylcholine from the exoplasmic to the cytosolic leaftlet of a membrane, using energy from the hydrolysis of ATP.
phosphatidylcholine floppase activity Catalysis of the movement of phosphatidylcholine from the cytosolic to the exoplasmic leaftlet of a membrane, using energy from the hydrolysis of ATP.
phosphatidylserine flippase activity Catalysis of the movement of phosphatidylserine from the exoplasmic to the cytosolic leaftlet of a membrane, using energy from the hydrolysis of ATP.
phosphatidylserine floppase activity Catalysis of the movement of phosphatidylserine from the cytosolic to the exoplasmic leaftlet of a membrane, using energy from the hydrolysis of ATP.

15 GO annotations of biological process

Name Definition
aminophospholipid transport The directed movement of aminophospholipids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Aminophospholipids contain phosphoric acid as a mono- or diester and an amino (NH2) group.
apical protein localization Any process in which a protein is transported to, or maintained in, apical regions of the cell.
bile acid and bile salt transport The directed movement of bile acid and bile salts into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
bile acid metabolic process The chemical reactions and pathways involving bile acids, a group of steroid carboxylic acids occurring in bile, where they are present as the sodium salts of their amides with glycine or taurine.
Golgi organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the Golgi apparatus.
inner ear receptor cell development The process whose specific outcome is the progression of an inner ear receptor cell over time, from its formation to the mature structure. Cell development does not include the steps involved in committing a cell to a specific fate.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
organic anion transport The directed movement of organic anions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Organic anions are atoms or small molecules with a negative charge which contain carbon in covalent linkage.
phospholipid translocation The movement of a phospholipid molecule from one leaflet of a membrane bilayer to the opposite leaflet.
regulation of chloride transport Any process that modulates the frequency, rate or extent of chloride transport.
regulation of microvillus assembly A process that modulates the formation of a microvillus.
regulation of plasma membrane organization Any process that modulates the frequency, rate or extent of plasma membrane organization.
sensory perception of sound The series of events required for an organism to receive an auditory stimulus, convert it to a molecular signal, and recognize and characterize the signal. Sonic stimuli are detected in the form of vibrations and are processed to form a sound.
vestibulocochlear nerve formation The process that gives rise to the vestibulocochlear nerve. This process pertains to the initial formation of a structure from unspecified parts. This sensory nerve innervates the membranous labyrinth of the inner ear. The vestibular branch innervates the vestibular apparatus that senses head position changes relative to gravity. The auditory branch innervates the cochlear duct, which is connected to the three bony ossicles which transduce sound waves into fluid movement in the cochlea.
xenobiotic transmembrane transport The process in which a xenobiotic, a compound foreign to the organim exposed to it, is transported across a membrane. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.

10 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9P241 ATP10D Phospholipid-transporting ATPase VD Homo sapiens (Human) PR
Q8TF62 ATP8B4 Probable phospholipid-transporting ATPase IM Homo sapiens (Human) PR
P98198 ATP8B2 Phospholipid-transporting ATPase ID Homo sapiens (Human) PR
Q9Y2Q0 ATP8A1 Phospholipid-transporting ATPase IA Homo sapiens (Human) PR
O43520 ATP8B1 Phospholipid-transporting ATPase IC Homo sapiens (Human) EV
P98199 Atp8b2 Phospholipid-transporting ATPase ID Mus musculus (Mouse) PR
P70704 Atp8a1 Phospholipid-transporting ATPase IA Mus musculus (Mouse) PR
D4AA47 Atp8b1 Phospholipid-transporting ATPase IC Rattus norvegicus (Rat) SS
Q9U280 tat-1 Phospholipid-transporting ATPase tat-1 Caenorhabditis elegans PR
Q5BL50 atp8b1 Phospholipid-transporting ATPase IC Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
10 20 30 40 50 60
MSTERDSETT FDEESQPNDE VVPYSDDETE DELEDQGSTV EPEQNRVNRE AEKKRETFRK
70 80 90 100 110 120
DCTWQVKAND RKFHEQPHFM NTKFFCIKES KYASNAIKTY KYNGFTFLPM NLFEQFKRAA
130 140 150 160 170 180
NFYFLILLIL QAIPQISTLA WYTTLVPLLL VLGITAIKDL VDDVARHKMD KEINNRTCEV
190 200 210 220 230 240
IKDGRFKIIK WKDIQVGDVI RLKKNDFIPA DILLLSSSEP NSLCYVETAE LDGETNLKFK
250 260 270 280 290 300
MALEITDQYL QIEDNLATFD GFIECEEPNN RLDKFTGTLF WKNQSFPLDA DKILLRGCVI
310 320 330 340 350 360
RNTDVCHGLV IFAGADTKIM KNSGKTRFKR TKIDYLMNYM VYTIFIVLIL VSAGLAIGHA
370 380 390 400 410 420
YWEAQVGNYS WYLYDGENAT PSYRGFLNFW GYIIVLNTMV PISLYVSVEV IRLGQSHFIN
430 440 450 460 470 480
WDLQMYYAEK DTPAKARTTT LNEQLGQIHY IFSDKTGTLT QNIMTFKKCC INGTIYGDHR
490 500 510 520 530 540
DASQHSHSKI ELVDFSWNTF ADGKLAFYDH YLIEQIQSGK EPEVRQFFFL LSICHTVMVD
550 560 570 580 590 600
RIDGQINYQA ASPDEGALVN AARNFGFAFL ARTQNTITVS ELGSERTYNV LAILDFNSDR
610 620 630 640 650 660
KRMSIIVRTP EGSIRLYCKG ADTVIYERLH RMNPTKQETQ DALDIFASET LRTLCLCYKE
670 680 690 700 710 720
IEEKEFTEWN NKFMAASVAS SNRDEALDKV YEEIEKDLIL LGATAIEDKL QDGVPETISK
730 740 750 760 770 780
LAKADIKIWV LTGDKKETAE NIGFACELLT EDTTICYGED INSLLHTRME NQRNRGGVSA
790 800 810 820 830 840
KFAPPVYEPF FPPGENRALI ITGSWLNEIL LEKKTKRSKI LKLKFPRTEE ERRMRSQSRR
850 860 870 880 890 900
RLEEKKEQRQ KNFVDLACEC SAVICCRVTP KQKAMVVDLV KRYKKAITLA IGDGANDVNM
910 920 930 940 950 960
IKTAHIGVGI SGQEGMQAVM SSDYSFAQFR YLQRLLLVHG RWSYIRMCKF LRYFFYKNFA
970 980 990 1000 1010 1020
FTLVHFWYSF FNGYSAQTAY EDWFITLYNV LYSSLPVLLM GLLDQDVSDK LSLRFPGLYV
1030 1040 1050 1060 1070 1080
VGQRDLLFNY KRFFVSLLHG VLTSMVLFFI PLGAYLQTVG QDGEAPSDYQ SFAVTVASAL
1090 1100 1110 1120 1130 1140
VITVNFQIGL DTSYWTFVNA FSIFGSIALY FGIMFDFHSA GIHVLFPSAF QFTGTASNAL
1150 1160 1170 1180 1190 1200
RQPYIWLTII LTVAVCLLPV VAIRFLSMTI WPSESDKIQK HRKRLKAEEQ WKRRQSVFRR
1210 1220 1230 1240 1250
GVSSRRSAYA FSHQRGYADL ISSGRSIRKK RSPLDAIIAD GTAEYRRTVE S