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Details on Person UniProt:P01116-2 KRAS
| Class:Id | ReferenceIsoform:152763 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:1-186 added on Sat February 7 2015;chain:2-186 added on Sat February 7 2015;propeptide:187-189 added on Sat February 7 2015;initiator methionine:1 for 152763 removed on Fri Nov 03 2023;initiator methionine: for 152763 added on Fri Nov 03 2023;initiator methionine: for 152763 removed on Fri Aug 15 2025;initiator methionine:1 for 152763 added on Fri Aug 15 2025 |
| _displayName | UniProt:P01116-2 KRAS |
| _timestamp | 2026-02-20 22:03:14 |
| chain | chain:1-186 initiator methionine:1 chain:2-186 propeptide:187-189 |
| checksum | 973547B2E11C2C81 |
| comment | FUNCTION Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Plays an important role in the regulation of cell proliferation (PubMed:22711838, PubMed:23698361). Activates MAPK1/MAPK3 resulting in phosphorylation and ultimately degradation of GJA1 (By similarity). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306).CATALYTIC ACTIVITY GTP + H2O = GDP + phosphate + H(+)ACTIVITY REGULATION Alternates between an inactive form bound to GDP and an active form bound to GTP (PubMed:22566140, PubMed:22431598, PubMed:39809765). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP) (PubMed:22711838). Interaction with SOS1 promotes exchange of bound GDP to GTP (PubMed:22566140, PubMed:22431598, PubMed:39809765).SUBUNIT Interacts with PHLPP (By similarity). Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts (when farnesylated) with PDE6D; this promotes dissociation from the cell membrane (PubMed:23698361). Interacts with SOS1 (PubMed:22431598). Interacts (when farnesylated) with GPR31 (PubMed:28619714). Interacts with RAP1GDS1 (PubMed:20709748, PubMed:24415755). Interacts (active GTP-bound form) with both SHOC2 and PP1c (all isoforms) to form a tertiary complex; SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Interacts (GTP-bound form) with MAPKAP1/SIN1; inhibiting K-Ras/KRAS activity (PubMed:34380736, PubMed:35522713).SUBUNIT Interacts with GPR31; in a farnelysation-dependent manner.INTERACTION Isoforms differ in the C-terminal region which is encoded by two alternative exons (IVA and IVB).PTM Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).PTM Palmitoylated at Lys-182, Lys-184 and Lys-185 (PubMed:29239724). Palmitoylation on lysine residues is promoted by palmitoylation at Cys-180 (PubMed:29239724). Lysine-depalmitoylation by SIRT2 promotes its localization to endomembranes in endocytic pathways (PubMed:29239724).PTM Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at Lys-170 in a non-degradative manner, leading to inhibit Ras signaling by decreasing Ras association with membranes.PTM (Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin TcsL.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE KRAS mutations are involved in cancer development.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the small GTPase superfamily. Ras family. |
| description | recommendedName: GTPase KRas ecNumber evidence="17 40"3.6.5.2 alternativeName: K-Ras 2 alternativeName: Ki-Ras alternativeName: c-K-ras alternativeName: c-Ki-ras component recommendedName: GTPase KRas, N-terminally processed /component |
| geneName | KRAS KRAS2 RASK2 |
| identifier | P01116 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Cardiomyopathy Cell membrane Cytoplasm Deafness Direct protein sequencing Disease variant Ectodermal dysplasia Glycoprotein GTP-binding Hydrolase Intellectual disability Isopeptide bond Lipoprotein Membrane Methylation Nucleotide-binding Palmitate Prenylation Proteomics identification Proto-oncogene Reference proteome Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | KRAS |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990934] ENSEMBL:ENSG00000133703 KRAS [Homo sapiens] |
| secondaryIdentifier | RASK_HUMAN A8K8Z5 B0LPF9 P01118 Q96D10 |
| sequenceLength | 189 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P01116-2 |
| (referenceEntity) | [EntityWithAccessionedSequence:9647815] S-Farn-Me KRAS4B [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9649686] pro-KRAS4B [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9649690] S-Farn-Me KRAS4B [endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:9649693] S-Farn proKRAS4B [endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:9649698] S-Farn KRAS4B [endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:9653482] pS181-S-Farn-Me KRAS4B [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9653578] pS181-S-Farn-Me KRAS4B [mitochondrial outer membrane] [Homo sapiens] [EntityWithAccessionedSequence:9654510] S-Farn-Me KRAS4B [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:9647814] S-farnesyl-L-cysteine methyl ester at 185 [GroupModifiedResidue:9649525] S-farnesyl-L-cysteine (farnesyl group) at 185 [ModifiedResidue:9653468] O-phospho-L-serine at 181 |
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No pathways have been reviewed or authored by UniProt:P01116-2 KRAS (152763)
