Protein: Calmodulin-regulated spectrin-associated protein 2 (Calmodulin-regulated spectrin-associated protein 1-like protein 1) (Q08AD1)
Organism: Homo sapiens (Human)
Function: Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization. Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization. Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization. In addition, it also reduces the velocity of microtubule polymerization. Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes. Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation. Through the microtubule cytoskeleton, regulates the autophagosome transport.
Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919, ECO:0000269|PubMed:24908486, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28814570}. Golgi apparatus {ECO:0000269|PubMed:27666745}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q8C1B1}. Cytoplasm {ECO:0000250|UniProtKB:Q8C1B1}. Note=Associated with the minus-end of microtubules and also detected at the centrosomes (PubMed:23169647, PubMed:24486153, PubMed:24706919, PubMed:24908486, PubMed:27666745, PubMed:28814570). Decorates the minus-end of microtubules by decreasing the rate of tubulin incorporation and remaining bound (PubMed:24486153). The length of CAMSAP2-decorated stretches on the minus-end of microtubules depends on MAPRE1/EB1 and MAPRE3/EB3, which promote elongation of CAMSAP2-decorated microtubule stretches (PubMed:28814570). Recruited to the Golgi apparatus by AKAP9 and PDE4DIP isoform 13/MMG8/SMYLE (PubMed:27666745). In neurons, localizes to the minus-end of microtubules in axon and dendrites (PubMed:24908486). {ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28814570}.
InterPro domains:
- IPR036872: CH domain superfamily (homologous_superfamily) [235-335]
- IPR011033: PRC-barrel-like superfamily (homologous_superfamily) [1345-1483]
- IPR058042: CASAMP, N-terminal domain (domain) [16-150]
- IPR014797: CAMSAP, CKK domain (domain) [1348-1483]
- IPR031372: CAMSAP, spectrin and Ca2+/calmodulin-binding region (conserved_site) [753-804]
- IPR032940: Calmodulin-regulated spectrin-associated protein (family) [1-1483]
- IPR038209: CKK domain superfamily (homologous_superfamily) [1358-1476]
- IPR022613: CASAMP, second calponin-homology domain (domain) [237-315]
- IPR001715: Calponin homology domain (domain) [222-335]
Sequence:
MGDAADPREMRKTFIVPAIKPFDHYDFSRAKIACNLAWLVAKAFGTENVPEELQEPFYTDQYDQEHIKPPVVNLLLSAELYCRAGSLILKSDAAKPLLGHDAVIQALAQKGLYVTDQEKLVTERDLHKKPIQMSAHLAMIDTLMMAYTVEMVSIEKVIACAQQYSAFFQATDLPYDIEDAVMYWINKVNEHLKDIMEQEQKLKEHHTVEAPGGQKSPSKWFWKLVPARYRKEQTLLKQLPCIPLVENLLKDGTDGCALAALIHFYCPDVVRLEDICLKETMSLADSLYNLQLIQEFCQEYLNQCCHFTLEDMLYAASSIKSNYLVFMAELFWWFEVVKPSFVQPRVVRPQGAEPVKDMPSIPVLNAAKRNVLDSSSDFPSSGEGATFTQSHHHLPSRYSRPQAHSSASGGIRRSSSMSYVDGFIGTWPKEKRSSVHGVSFDISFDKEDSVQRSTPNRGITRSISNEGLTLNNSHVSKHIRKNLSFKPINGEEEAESIEEELNIDSHSDLKSCVPLNTNELNSNENIHYKLPNGALQNRILLDEFGNQIETPSIEEALQIIHDTEKSPHTPQPDQIANGFFLHSQEMSILNSNIKLNQSSPDNVTDTKGALSPITDNTEVDTGIHVPSEDIPETMDEDSSLRDYTVSLDSDMDDASKFLQDYDIRTGNTREALSPCPSTVSTKSQPGSSASSSSGVKMTSFAEQKFRKLNHTDGKSSGSSSQKTTPEGSELNIPHVVAWAQIPEETGLPQGRDTTQLLASEMVHLRMKLEEKRRAIEAQKKKMEAAFTKQRQKMGRTAFLTVVKKKGDGISPLREEAAGAEDEKVYTDRAKEKESQKTDGQRSKSLADIKESMENPQAKWLKSPTTPIDPEKQWNLASPSEETLNEGEILEYTKSIEKLNSSLHFLQQEMQRLSLQQEMLMQMREQQSWVISPPQPSPQKQIRDFKPSKQAGLSSAIAPFSSDSPRPTHPSPQSSNRKSASFSVKSQRTPRPNELKITPLNRTLTPPRSVDSLPRLRRFSPSQVPIQTRSFVCFGDDGEPQLKESKPKEEVKKEELESKGTLEQRGHNPEEKEIKPFESTVSEVLSLPVTETVCLTPNEDQLNQPTEPPPKPVFPPTAPKNVNLIEVSLSDLKPPEKADVPVEKYDGESDKEQFDDDQKVCCGFFFKDDQKAENDMAMKRAALLEKRLRREKETQLRKQQLEAEMEHKKEETRRKTEEERQKKEDERARREFIRQEYMRRKQLKLMEDMDTVIKPRPQVVKQKKQRPKSIHRDHIESPKTPIKGPPVSSLSLASLNTGDNESVHSGKRTPRSESVEGFLSPSRCGSRNGEKDWENASTTSSVASGTEYTGPKLYKEPSAKSNKHIIQNALAHCCLAGKVNEGQKKKILEEMEKSDANNFLILFRDSGCQFRSLYTYCPETEEINKLTGIGPKSITKKMIEGLYKYNSDRKQFSHIPAKTLSASVDAITIHSHLWQTKRPVTPKKLLPTKA
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0044877 (protein-containing complex binding), GO:0005515 (protein binding), GO:0030507 (spectrin binding), GO:0008092 (cytoskeletal protein binding), GO:0015631 (tubulin binding), GO:0008017 (microtubule binding)
Biological Process (BP): GO:0008150 (biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0009653 (anatomical structure morphogenesis), GO:0007163 (establishment or maintenance of cell polarity), GO:0007155 (cell adhesion), GO:0071840 (cellular component organization or biogenesis), GO:0050794 (regulation of cellular process), GO:0007017 (microtubule-based process), GO:0040012 (regulation of locomotion), GO:0061339 (establishment or maintenance of monopolar cell polarity), GO:0048729 (tissue morphogenesis), GO:0030010 (establishment of cell polarity), GO:2000145 (regulation of cell motility), GO:0098609 (cell-cell adhesion), GO:0030154 (cell differentiation), GO:0030155 (regulation of cell adhesion), GO:0000226 (microtubule cytoskeleton organization), GO:0032886 (regulation of microtubule-based process), GO:0044087 (regulation of cellular component biogenesis), GO:0009888 (tissue development), GO:0061245 (establishment or maintenance of bipolar cell polarity), GO:0016043 (cellular component organization), GO:0030952 (establishment or maintenance of cytoskeleton polarity), GO:0051128 (regulation of cellular component organization), GO:0043254 (regulation of protein-containing complex assembly), GO:0030951 (establishment or maintenance of microtubule cytoskeleton polarity), GO:0010810 (regulation of cell-substrate adhesion), GO:1901888 (regulation of cell junction assembly), GO:0035088 (establishment or maintenance of apical/basal cell polarity), GO:0043954 (cellular component maintenance), GO:0002009 (morphogenesis of an epithelium), GO:0030334 (regulation of cell migration), GO:0090162 (establishment of epithelial cell polarity), GO:0061162 (establishment of monopolar cell polarity), GO:0150116 (regulation of cell-substrate junction organization), GO:0030855 (epithelial cell differentiation), GO:1902903 (regulation of supramolecular fiber organization), GO:0070507 (regulation of microtubule cytoskeleton organization), GO:0034453 (microtubule anchoring), GO:0090136 (epithelial cell-cell adhesion), GO:0033043 (regulation of organelle organization), GO:0060429 (epithelium development), GO:0006996 (organelle organization), GO:0034330 (cell junction organization), GO:0051493 (regulation of cytoskeleton organization), GO:0035089 (establishment of apical/basal cell polarity), GO:0032271 (regulation of protein polymerization), GO:0031113 (regulation of microtubule polymerization), GO:0001952 (regulation of cell-matrix adhesion), GO:0034331 (cell junction maintenance), GO:0030859 (polarized epithelial cell differentiation), GO:0007010 (cytoskeleton organization), GO:0090109 (regulation of cell-substrate junction assembly), GO:0031110 (regulation of microtubule polymerization or depolymerization), GO:0001738 (morphogenesis of a polarized epithelium), GO:0045197 (establishment or maintenance of epithelial cell apical/basal polarity), GO:0045198 (establishment of epithelial cell apical/basal polarity), GO:1903358 (regulation of Golgi organization), GO:0045216 (cell-cell junction organization), GO:0034332 (adherens junction organization), GO:0045217 (cell-cell junction maintenance), GO:0051893 (regulation of focal adhesion assembly), GO:0034334 (adherens junction maintenance)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:1990752 (microtubule end), GO:0099080 (supramolecular complex), GO:0099081 (supramolecular polymer), GO:0043229 (intracellular organelle), GO:0043228 (non-membrane-bounded organelle), GO:0099512 (supramolecular fiber), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0005856 (cytoskeleton), GO:0099513 (polymeric cytoskeletal fiber), GO:0005874 (microtubule), GO:0015630 (microtubule cytoskeleton)