Protein: Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] (P02545)
Organism: Homo sapiens (Human)
Function: Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation. Required for osteoblastogenesis and bone formation. Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone. Required for cardiac homeostasis.
Subcellular location: Nucleus lamina {ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547, ECO:0000305|PubMed:10080180}. Nucleus envelope {ECO:0000269|PubMed:29599122, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}. Nucleus, nucleoplasm {ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:31548606}. Nucleus matrix {ECO:0000269|PubMed:31548606}. Note=Farnesylation of prelamin-A/C facilitates nuclear envelope targeting and subsequent cleavage by ZMPSTE24/FACE1 to remove the farnesyl group produces mature lamin-A/C, which can then be inserted into the nuclear lamina (PubMed:15317753). EMD is required for proper localization of non-farnesylated prelamin-A/C (PubMed:19323649). Also localizes to the micronuclear envelope in response to response to genome instability (PubMed:37788673). {ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:19323649, ECO:0000269|PubMed:37788673}.; SUBCELLULAR LOCATION: [Isoform C]: Nucleus speckle {ECO:0000269|PubMed:16061563}.
InterPro domains:
- IPR001322: Lamin tail domain (domain) [428-545]
- IPR018039: Intermediate filament protein, conserved site (conserved_site) [373-381]
- IPR036415: Lamin tail domain superfamily (homologous_superfamily) [401-550]
- IPR039008: Intermediate filament, rod domain (domain) [30-387]
Sequence:
METPSQRRATRSGAQASSTPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAAYEAELGDARKTLDSVAKERARLQLELSKVREEFKELKARNTKKEGDLIAAQARLKDLEALLNSKEAALSTALSEKRTLEGELHDLRGQVAKLEAALGEAKKQLQDEMLRRVDAENRLQTMKEELDFQKNIYSEELRETKRRHETRLVEIDNGKQREFESRLADALQELRAQHEDQVEQYKKELEKTYSAKLDNARQSAERNSNLVGAAHEELQQSRIRIDSLSAQLSQLQKQLAAKEAKLRDLEDSLARERDTSRRLLAEKEREMAEMRARMQQQLDEYQELLDIKLALDMEIHAYRKLLEGEEERLRLSPSPTSQRSRGRASSHSSQTQGGGSVTKKRKLESTESRSSFSQHARTSGRVAVEEVDEEGKFVRLRNKSNEDQSMGNWQIKRQNGDDPLLTYRFPPKFTLKAGQVVTIWAAGAGATHSPPTDLVWKAQNTWGCGNSLRTALINSTGEEVAMRKLVRSVTVVEDDEDEDGDDLLHHHHGSHCSSSGDPAEYNLRSRTVLCGTCGQPADKASASGSGAQVGGPISSGSSASSVTVTRSYRSVGGSGGGSFGDNLVTRSYLLGNSSPRTQSPQNCSIM
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005198 (structural molecule activity), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0048522 (positive regulation of cellular process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0044085 (cellular component biogenesis), GO:0042127 (regulation of cell population proliferation), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0008285 (negative regulation of cell population proliferation), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0008284 (positive regulation of cell population proliferation), GO:0042127 (regulation of cell population proliferation), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0043933 (protein-containing complex organization), GO:0051252 (regulation of RNA metabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0010468 (regulation of gene expression), GO:0022607 (cellular component assembly), GO:0065003 (protein-containing complex assembly), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0065003 (protein-containing complex assembly), GO:2001141 (regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006357 (regulation of transcription by RNA polymerase II), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0045893 (positive regulation of DNA-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0065004 (protein-DNA complex assembly), GO:0045892 (negative regulation of DNA-templated transcription), GO:0045944 (positive regulation of transcription by RNA polymerase II), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005654 (nucleoplasm), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0043229 (intracellular organelle), GO:0016607 (nuclear speck), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043231 (intracellular membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)