Reviewed,
UniProtKB/Swiss-Prot P21359 (NF1_HUMAN)
Last modified
November 25, 2008.
Version 112.
History...
Clusters with 100%,
90%,
50% identity |
 Documents (6) |
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Names and origin
| Protein names | Recommended name: Neurofibromin Alternative name(s): Neurofibromatosis-related protein NF-1 Cleaved into the following chain: 1- Recommended name: Neurofibromin truncated | ||
| Gene names |
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| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 2839 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity. |
| Involvement in disease | Defects in NF1 are the cause of type 1 neurofibromatosis (NF1) [MIM:162200]; also called Von Recklinghausen syndrome. NF1 is one of the most frequent autosomal dominant diseases (about 1 in 3000). It exhibits full penetrance by the age of 5 years and high mutation rate with 30 to 50% of NF1 patients representing a new mutation. Among the many clinical features of NF1 are patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, peripheral nervous system associated tumors and fibromatous skin tumors. Defects in NF1 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Germline mutations of NF1 account for the association of JMML with type 1 neurofibromatosis (NF1). Defects in NF1 are the cause of Watson syndrome (WS) [MIM:193520]. WS is characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and mental retardation. WS is considered as an atypical form of NF1. Defects in NF1 are a cause of familial spinal neurofibromatosis (spinal NF) [MIM:162210]. Familial spinal NF is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors. Defects in NF1 are a cause of neurofibromatosis-Noonan syndrome (NFNS) [MIM:601321]. NFNS is characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Defects in NF1 may be a cause of colorectal cancer (CRC) [MIM:114500]. |
| Sequence similarities | Contains 1 CRAL-TRIO domain. Contains 1 Ras-GAP domain. |
| Caution | Was originally (Ref.33) thought to be associated with LEOPARD (LS), an autosomal dominant syndrome. |
| RNA editing | Edited at position 1306. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] Notes: Experimental confirmation may be lacking for some isoforms. | ||||||
| Isoform 2 (identifier: P21359-1) Also known as: Type II; 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. | ||||||
| Isoform 1 (identifier: P21359-2) Also known as: Type I; The sequence of this isoform differs from the canonical sequence as follows: 1371-1391: Missing. | ||||||
| Isoform 3 (identifier: P21359-3) The sequence of this isoform differs from the canonical sequence as follows: 548-551: ALLV → VRGK 552-2839: Missing. | ||||||
| Isoform 4 (identifier: P21359-4) The sequence of this isoform differs from the canonical sequence as follows: 1591-1598: SIFYQAGT → TPPPEPET 1599-2839: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed By similarity | ||||||
| Chain | 2 – 2839 | 2838 | Neurofibromin | PRO_0000010773 | |||||
| Chain | 2 – 1305 | 1304 | Neurofibromin truncated | PRO_0000010774 | |||||
Regions | |||||||||
| Domain | 1235 – 1451 | 217 | Ras-GAP | ||||||
| Domain | 1580 – 1738 | 159 | CRAL-TRIO | ||||||
| Compositional bias | 1352 – 1355 | 4 | Poly-Ser | ||||||
Amino acid modifications | |||||||||
| Modified residue | 2 | 1 | N-acetylalanine By similarity | ||||||
| Modified residue | 864 | 1 | Phosphoserine | ||||||
| Modified residue | 2188 | 1 | Phosphoserine | ||||||
| Modified residue | 2476 | 1 | Phosphotyrosine | ||||||
| Modified residue | 2514 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 2515 | 1 | Phosphoserine | ||||||
| Modified residue | 2577 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 2829 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Alternative sequence | 548 – 551 | 4 | ALLV → VRGK in isoform 3. | VSP_001629 | |||||
| Alternative sequence | 552 – 2839 | 2288 | Missing in isoform 3. | VSP_001630 | |||||
| Alternative sequence | 1371 – 1391 | 21 | Missing in isoform 1. | VSP_001628 | |||||
| Alternative sequence | 1591 – 1598 | 8 | SIFYQAGT → TPPPEPET in isoform 4. | VSP_001631 | |||||
| Alternative sequence | 1599 – 2839 | 1241 | Missing in isoform 4. | VSP_001632 | |||||
| Natural variant | 31 | 1 | H → R in NF1. | VAR_032459 | |||||
| Natural variant | 74 | 1 | A → D in mismatch repair deficient cancer cells. | VAR_017550 | |||||
| Natural variant | 80 | 1 | Y → C | VAR_022254 | |||||
| Natural variant | 82 | 1 | S → F in NF1. | VAR_021730 | |||||
| Natural variant | 93 | 1 | C → Y in NF1. | VAR_017551 | |||||
| Natural variant | 117 | 1 | I → S in NF1. | VAR_010989 | |||||
| Natural variant | 145 | 1 | L → P in NF1. | VAR_032460 | |||||
| Natural variant | 157 | 1 | I → N in NF1. | VAR_021731 | |||||
| Natural variant | 176 | 1 | D → E in mismatch repair deficient cancer cells; polymorphism. | VAR_017552 | |||||
| Natural variant | 186 | 1 | D → V in NF1; reduced splicing enhancement. | VAR_032461 | |||||
| Natural variant | 194 | 1 | L → R in NFNS. | VAR_032462 | |||||
| Natural variant | 216 | 1 | L → P in NF1. | VAR_021732 | |||||
| Natural variant | 324 | 1 | C → R in NF1. | VAR_032463 | |||||
| Natural variant | 337 | 1 | E → V in NF1. | VAR_032464 | |||||
| Natural variant | 338 | 1 | D → G in NF1. | VAR_010990 | |||||
| Natural variant | 357 | 1 | L → P in NF1. | VAR_021733 | |||||
| Natural variant | 489 | 1 | Y → C in NF1. | VAR_032465 | |||||
| Natural variant | 491 | 1 | Y → C in NF1. | VAR_021734 | |||||
| Natural variant | 508 | 1 | L → P in NF1. | VAR_010991 | |||||
| Natural variant | 532 | 1 | L → P in NF1. | VAR_032466 | |||||
| Natural variant | 549 | 1 | L → P in NF1. | VAR_021735 | |||||
| Natural variant | 574 | 1 | S → R in NF1. | VAR_032467 | |||||
| Natural variant | 578 | 1 | L → R in NF1. | VAR_021736 | |||||
| Natural variant | 581 | 1 | I → T in NF1. | VAR_021737 | |||||
| Natural variant | 583 | 1 | K → R in NF1. | VAR_021738 | |||||
| Natural variant | 604 | 1 | L → V in NF1. | VAR_017553 | |||||
| Natural variant | 629 | 1 | G → R in NF1. | VAR_002653 | |||||
| Natural variant | 665 | 1 | S → F in NF1; unknown pathological significance. | VAR_021739 | |||||
| Natural variant | 678 | 1 | P → L: dbSNP rs17881753. | VAR_022255 | |||||
| Natural variant | 695 | 1 | L → P in NF1. | VAR_021740 | |||||
| Natural variant | 712 | 1 | H → R in mismatch repair deficient cancer cells. | VAR_017554 | |||||
| Natural variant | 763 | 1 | L → P in NF1. | VAR_021741 | |||||
| Natural variant | 765 | 1 | R → H | VAR_021742 | |||||
| Natural variant | 777 | 1 | W → S in NF1. | VAR_021743 | |||||
| Natural variant | 780 | 1 | T → K in NF1. | VAR_021744 | |||||
| Natural variant | 781 | 1 | H → P in NF1. | VAR_021745 | |||||
| Natural variant | 784 | 1 | W → C in NF1. | VAR_021746 | |||||
| Natural variant | 784 | 1 | W → R in NF1. | VAR_021747 | |||||
| Natural variant | 844 | 1 | L → F in NF1. | VAR_010992 | |||||
| Natural variant | 844 | 1 | L → P in NF1. | VAR_032468 | |||||
| Natural variant | 844 | 1 | L → R in NF1; sporadic. | VAR_002654 | |||||
| Natural variant | 847 | 1 | L → P in NF1. | VAR_021748 | |||||
| Natural variant | 848 | 1 | G → E in NF1. | VAR_021749 | |||||
| Natural variant | 873 | 1 | R → C in NF1. | VAR_032469 | |||||
| Natural variant | 898 | 1 | L → P in NF1; sporadic. | VAR_002655 | |||||
| Natural variant | 920 | 1 | L → P in NF1; patient with cafe-au-lait spots; may be a distinct form of NF1. | VAR_021750 | |||||
| Natural variant | 968 | 1 | M → R in NF1. | VAR_021751 | |||||
| Natural variant | 991 | 1 | Missing in NF1. | VAR_002656 | |||||
| Natural variant | 1035 | 1 | M → R in NF1. | VAR_002657 | |||||
| Natural variant | 1073 | 1 | M → V in NF1. | VAR_032470 | |||||
| Natural variant | 1147 | 1 | L → P in NF1. | VAR_021752 | |||||
| Natural variant | 1156 | 1 | N → S in NF1. | VAR_021753 | |||||
| Natural variant | 1166 | 1 | G → D in NF1. | VAR_010993 | |||||
| Natural variant | 1187 | 1 | L → I in a colorectal cancer sample; somatic mutation. | VAR_035543 | |||||
| Natural variant | 1193 | 1 | F → C in NF1. | VAR_021754 | |||||
| Natural variant | 1196 | 1 | L → R in NF1. | VAR_032471 | |||||
| Natural variant | 1204 | 1 | R → G in NF1. | ||||||