ID ASPM_HUMAN Reviewed; 3477 AA. AC Q8IZT6; Q4G1H1; Q5VYL3; Q86UX4; Q8IUL2; Q8IZJ7; Q8IZJ8; Q8IZJ9; Q8N4D1; AC Q9NVS1; Q9NVT6; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 27-MAR-2024, entry version 190. DE RecName: Full=Abnormal spindle-like microcephaly-associated protein; DE AltName: Full=Abnormal spindle protein homolog; DE Short=Asp homolog; GN Name=ASPM; Synonyms=MCPH5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INVOLVEMENT IN MCPH5, AND RP VARIANT HIS-2494. RC TISSUE=Colon adenocarcinoma, and Fetal brain; RX PubMed=12355089; DOI=10.1038/ng995; RA Bond J., Roberts E., Mochida G.H., Hampshire D.J., Scott S., Askham J.M., RA Springell K., Mahadevan M., Crow Y.J., Markham A.F., Walsh C.A., RA Woods C.G.; RT "ASPM is a major determinant of cerebral cortical size."; RL Nat. Genet. 32:316-320(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HIS-2494. RX PubMed=14704186; DOI=10.1093/genetics/165.4.2063; RA Zhang J.; RT "Evolution of the human ASPM gene, a major determinant of brain size."; RL Genetics 165:2063-2070(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ALTERNATIVE SPLICING, AND RP SUBCELLULAR LOCATION. RX PubMed=15972725; DOI=10.1093/hmg/ddi220; RA Kouprina N., Pavlicek A., Collins N.K., Nakano M., Noskov V.N., RA Ohzeki J.I., Mochida G.H., Risinger J.I., Goldsmith P., Gunsior M., RA Solomon G., Gersch W., Kim J.H., Barrett J.C., Walsh C.A., Jurka J., RA Masumoto H., Larionov V.; RT "The microcephaly ASPM gene is expressed in proliferating tissues and RT encodes for a mitotic spindle protein."; RL Hum. Mol. Genet. 14:2155-2165(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-147 AND 709-3477 (ISOFORM 2), RP AND VARIANT PHE-1090. RC TISSUE=Kidney, and Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2740-3477 (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP INVOLVEMENT IN MCPH5, AND VARIANTS GLY-2562; ILE-2647 AND ARG-3132. RX PubMed=14574646; DOI=10.1086/379085; RA Bond J., Scott S., Hampshire D.J., Springell K., Corry P., Abramowicz M.J., RA Mochida G.H., Hennekam R.C.M., Maher E.R., Fryns J.-P., Alswaid A., RA Jafri H., Rashid Y., Mubaidin A., Walsh C.A., Roberts E., Woods C.G.; RT "Protein-truncating mutations in ASPM cause variable reduction in brain RT size."; RL Am. J. Hum. Genet. 73:1170-1177(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-392, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280; SER-283; SER-425 AND RP SER-1103, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367 AND SER-392, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280; SER-283 AND SER-392, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP INVOLVEMENT IN MCPH5. RX PubMed=22989186; DOI=10.1111/j.1399-0004.2012.01949.x; RA Papari E., Bastami M., Farhadi A., Abedini S.S., Hosseini M., Bahman I., RA Mohseni M., Garshasbi M., Moheb L.A., Behjati F., Kahrizi K., Ropers H.H., RA Najmabadi H.; RT "Investigation of primary microcephaly in Bushehr province of Iran: novel RT STIL and ASPM mutations."; RL Clin. Genet. 83:488-490(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-425; SER-605 AND RP SER-1103, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP FUNCTION, INTERACTION WITH KATNA1 AND KATNB1, AND SUBCELLULAR LOCATION. RX PubMed=28436967; DOI=10.1038/ncb3511; RA Jiang K., Rezabkova L., Hua S., Liu Q., Capitani G., Maarten Altelaar A.F., RA Heck A.J.R., Kammerer R.A., Steinmetz M.O., Akhmanova A.; RT "Microtubule minus-end regulation at spindle poles by an ASPM-katanin RT complex."; RL Nat. Cell Biol. 19:480-492(2017). RN [17] RP VARIANTS HIS-2494; ASP-2526; ILE-2647 AND PRO-3180. RX PubMed=16673149; DOI=10.1007/s10048-006-0042-4; RA Gul A., Hassan M.J., Mahmood S., Chen W., Rahmani S., Naseer M.I., RA Dellefave L., Muhammad N., Rafiq M.A., Ansar M., Chishti M.S., Ali G., RA Siddique T., Ahmad W.; RT "Genetic studies of autosomal recessive primary microcephaly in 33 RT Pakistani families: Novel sequence variants in ASPM gene."; RL Neurogenetics 7:105-110(2006). RN [18] RP VARIANT ILE-2647. RX PubMed=18204051; DOI=10.1093/hmg/ddn021; RA Wang J.-K., Li Y., Su B.; RT "A common SNP of MCPH1 is associated with cranial volume variation in RT Chinese population."; RL Hum. Mol. Genet. 17:1329-1335(2008). RN [19] RP VARIANT PRO-3180. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). CC -!- FUNCTION: Involved in mitotic spindle regulation and coordination of CC mitotic processes. The function in regulating microtubule dynamics at CC spindle poles including spindle orientation, astral microtubule density CC and poleward microtubule flux seems to depend on the association with CC the katanin complex formed by KATNA1 and KATNB1. Enhances the CC microtubule lattice severing activity of KATNA1 by recruiting the CC katanin complex to microtubules. Can block microtubule minus-end growth CC and reversely this function can be enhanced by the katanin complex CC (PubMed:28436967). May have a preferential role in regulating CC neurogenesis. {ECO:0000269|PubMed:12355089, CC ECO:0000269|PubMed:15972725, ECO:0000269|PubMed:28436967}. CC -!- SUBUNIT: Interacts with KATNA1 and KATNB1; katanin complex formation CC KATNA1:KATNB1 is required for the association. CC {ECO:0000269|PubMed:28436967}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton, CC spindle {ECO:0000269|PubMed:15972725}. Nucleus {ECO:0000250}. Note=The CC nuclear-cytoplasmic distribution could be regulated by the availability CC of calmodulin (By similarity). Localizes to spindle poles during CC mitosis (PubMed:19690332). Associates with microtubule minus ends (By CC similarity). {ECO:0000250|UniProtKB:Q8CJ27}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8IZT6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IZT6-2; Sequence=VSP_010680; CC -!- DISEASE: Microcephaly 5, primary, autosomal recessive (MCPH5) CC [MIM:608716]: A disease defined as a head circumference more than 3 CC standard deviations below the age-related mean. Brain weight is CC markedly reduced and the cerebral cortex is disproportionately small. CC Despite this marked reduction in size, the gyral pattern is relatively CC well preserved, with no major abnormality in cortical architecture. CC Affected individuals are mentally retarded. Primary microcephaly is CC further defined by the absence of other syndromic features or CC significant neurological deficits due to degenerative brain disorder. CC {ECO:0000269|PubMed:12355089, ECO:0000269|PubMed:14574646, CC ECO:0000269|PubMed:22989186}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH34607.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA91676.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44463/ASPM"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF509326; AAN40011.1; -; mRNA. DR EMBL; AY099890; AAM44119.1; -; mRNA. DR EMBL; AY099891; AAM44120.1; -; mRNA. DR EMBL; AY099892; AAM44121.1; -; mRNA. DR EMBL; AY099893; AAM44122.1; -; mRNA. DR EMBL; AY101201; AAM48745.1; -; mRNA. DR EMBL; AY367065; AAR12641.1; -; mRNA. DR EMBL; AY971956; AAY46814.1; -; mRNA. DR EMBL; AL353809; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91274.1; -; Genomic_DNA. DR EMBL; BC015396; AAH15396.1; -; mRNA. DR EMBL; BC034607; AAH34607.1; ALT_INIT; mRNA. DR EMBL; AK001411; BAA91676.1; ALT_INIT; mRNA. DR CCDS; CCDS1389.1; -. [Q8IZT6-1] DR CCDS; CCDS55672.1; -. [Q8IZT6-2] DR RefSeq; NP_001193775.1; NM_001206846.1. [Q8IZT6-2] DR RefSeq; NP_060606.3; NM_018136.4. [Q8IZT6-1] DR SMR; Q8IZT6; -. DR BioGRID; 129236; 145. DR IntAct; Q8IZT6; 90. DR STRING; 9606.ENSP00000356379; -. DR CarbonylDB; Q8IZT6; -. DR GlyGen; Q8IZT6; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q8IZT6; -. DR PhosphoSitePlus; Q8IZT6; -. DR BioMuta; ASPM; -. DR DMDM; 215273935; -. DR EPD; Q8IZT6; -. DR jPOST; Q8IZT6; -. DR MassIVE; Q8IZT6; -. DR MaxQB; Q8IZT6; -. DR PaxDb; 9606-ENSP00000356379; -. DR PeptideAtlas; Q8IZT6; -. DR ProteomicsDB; 71424; -. [Q8IZT6-1] DR ProteomicsDB; 71425; -. [Q8IZT6-2] DR Pumba; Q8IZT6; -. DR Antibodypedia; 34476; 88 antibodies from 19 providers. DR DNASU; 259266; -. DR Ensembl; ENST00000294732.11; ENSP00000294732.7; ENSG00000066279.19. [Q8IZT6-2] DR Ensembl; ENST00000367409.9; ENSP00000356379.4; ENSG00000066279.19. [Q8IZT6-1] DR GeneID; 259266; -. DR KEGG; hsa:259266; -. DR MANE-Select; ENST00000367409.9; ENSP00000356379.4; NM_018136.5; NP_060606.3. DR UCSC; uc001gtu.4; human. [Q8IZT6-1] DR AGR; HGNC:19048; -. DR CTD; 259266; -. DR DisGeNET; 259266; -. DR GeneCards; ASPM; -. DR GeneReviews; ASPM; -. DR HGNC; HGNC:19048; ASPM. DR HPA; ENSG00000066279; Group enriched (bone marrow, lymphoid tissue). DR MalaCards; ASPM; -. DR MIM; 605481; gene. DR MIM; 608716; phenotype. DR neXtProt; NX_Q8IZT6; -. DR OpenTargets; ENSG00000066279; -. DR Orphanet; 2512; Autosomal recessive primary microcephaly. DR PharmGKB; PA38782; -. DR VEuPathDB; HostDB:ENSG00000066279; -. DR eggNOG; KOG0160; Eukaryota. DR eggNOG; KOG0165; Eukaryota. DR GeneTree; ENSGT00560000077332; -. DR HOGENOM; CLU_000237_0_0_1; -. DR InParanoid; Q8IZT6; -. DR OMA; CCCCYIF; -. DR OrthoDB; 53079at2759; -. DR PhylomeDB; Q8IZT6; -. DR TreeFam; TF351180; -. DR PathwayCommons; Q8IZT6; -. DR SignaLink; Q8IZT6; -. DR SIGNOR; Q8IZT6; -. DR BioGRID-ORCS; 259266; 117 hits in 1176 CRISPR screens. DR ChiTaRS; ASPM; human. DR GeneWiki; ASPM_(gene); -. DR GenomeRNAi; 259266; -. DR Pharos; Q8IZT6; Tbio. DR PRO; PR:Q8IZT6; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q8IZT6; Protein. DR Bgee; ENSG00000066279; Expressed in oocyte and 115 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0005813; C:centrosome; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0072687; C:meiotic spindle; IEA:Ensembl. DR GO; GO:0036449; C:microtubule minus-end; IDA:HGNC. DR GO; GO:0030496; C:midbody; IEA:Ensembl. DR GO; GO:0097431; C:mitotic spindle pole; IDA:HGNC. DR GO; GO:0005634; C:nucleus; IDA:HGNC. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0008356; P:asymmetric cell division; IEA:Ensembl. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0048589; P:developmental growth; IEA:Ensembl. DR GO; GO:0021873; P:forebrain neuroblast division; IEA:Ensembl. DR GO; GO:0051661; P:maintenance of centrosome location; IEA:Ensembl. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0090306; P:meiotic spindle assembly; IEA:Ensembl. DR GO; GO:0045769; P:negative regulation of asymmetric cell division; IEA:Ensembl. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEA:Ensembl. DR GO; GO:0048477; P:oogenesis; IEA:Ensembl. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:0051445; P:regulation of meiotic cell cycle; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR GO; GO:0051653; P:spindle localization; IMP:HGNC. DR GO; GO:0007051; P:spindle organization; IMP:HGNC. DR CDD; cd21223; CH_ASPM_rpt1; 1. DR CDD; cd21224; CH_ASPM_rpt2; 1. DR Gene3D; 1.20.5.190; -; 31. DR Gene3D; 1.10.418.10; Calponin-like domain; 2. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR031549; ASH. DR InterPro; IPR001715; CH_dom. DR InterPro; IPR036872; CH_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR000048; IQ_motif_EF-hand-BS. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR22706:SF1; ABNORMAL SPINDLE-LIKE MICROCEPHALY-ASSOCIATED PROTEIN ISOFORM X1; 1. DR PANTHER; PTHR22706; UNCHARACTERIZED; 1. DR Pfam; PF15780; ASH; 1. DR Pfam; PF00307; CH; 1. DR Pfam; PF00612; IQ; 39. DR SMART; SM00033; CH; 2. DR SMART; SM00015; IQ; 63. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF47576; Calponin-homology domain, CH-domain; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 18. DR PROSITE; PS50021; CH; 2. DR PROSITE; PS50096; IQ; 39. DR Genevisible; Q8IZT6; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calmodulin-binding; Cell cycle; Cell division; KW Coiled coil; Cytoplasm; Cytoskeleton; Disease variant; KW Intellectual disability; Mitosis; Nucleus; Phosphoprotein; KW Primary microcephaly; Reference proteome; Repeat. FT CHAIN 1..3477 FT /note="Abnormal spindle-like microcephaly-associated FT protein" FT /id="PRO_0000191332" FT DOMAIN 920..1056 FT /note="Calponin-homology (CH) 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 1110..1261 FT /note="Calponin-homology (CH) 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 1347..1378 FT /note="IQ 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1393..1422 FT /note="IQ 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1582..1613 FT /note="IQ 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1632..1661 FT /note="IQ 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1655..1684 FT /note="IQ 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1728..1757 FT /note="IQ 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1751..1782 FT /note="IQ 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1801..1830 FT /note="IQ 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1824..1853 FT /note="IQ 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1874..1903 FT /note="IQ 10" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1897..1928 FT /note="IQ 11" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1947..1978 FT /note="IQ 12" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 1970..2001 FT /note="IQ 13" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2020..2049 FT /note="IQ 14" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2043..2074 FT /note="IQ 15" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2093..2124 FT /note="IQ 16" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2116..2147 FT /note="IQ 17" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2166..2197 FT /note="IQ 18" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2189..2218 FT /note="IQ 19" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2239..2270 FT /note="IQ 20" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2262..2293 FT /note="IQ 21" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2311..2342 FT /note="IQ 22" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2334..2365 FT /note="IQ 23" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2384..2415 FT /note="IQ 24" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2407..2438 FT /note="IQ 25" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2457..2488 FT /note="IQ 26" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2530..2561 FT /note="IQ 27" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2624..2653 FT /note="IQ 28" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2665..2696 FT /note="IQ 29" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2688..2719 FT /note="IQ 30" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2738..2767 FT /note="IQ 31" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2859..2890 FT /note="IQ 32" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2909..2938 FT /note="IQ 33" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2932..2963 FT /note="IQ 34" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 2954..2985 FT /note="IQ 35" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 3029..3060 FT /note="IQ 36" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 3079..3110 FT /note="IQ 37" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 3181..3210 FT /note="IQ 38" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT DOMAIN 3204..3235 FT /note="IQ 39" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT REGION 1..30 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 308..409 FT /note="Sufficient for interaction with KATNA1:KATNB1" FT /evidence="ECO:0000250|UniProtKB:Q8CJ27" FT REGION 415..443 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 559..581 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 1057..1078 FT /evidence="ECO:0000255" FT COMPBIAS 559..574 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 280 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 283 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 367 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 392 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231" FT MOD_RES 425 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 605 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1103 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 1356..2940 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:15972725" FT /id="VSP_010680" FT VARIANT 313 FT /note="I -> V (in dbSNP:rs12025066)" FT /id="VAR_047263" FT VARIANT 430 FT /note="R -> G (in dbSNP:rs6428388)" FT /id="VAR_024369" FT VARIANT 869 FT /note="T -> S (in dbSNP:rs7551108)" FT /id="VAR_046758" FT VARIANT 1090 FT /note="S -> F (in dbSNP:rs16841081)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_046759" FT VARIANT 2494 FT /note="Y -> H (in dbSNP:rs964201)" FT /evidence="ECO:0000269|PubMed:12355089, FT ECO:0000269|PubMed:14704186, ECO:0000269|PubMed:16673149" FT /id="VAR_046760" FT VARIANT 2526 FT /note="N -> D (in dbSNP:rs587783267)" FT /evidence="ECO:0000269|PubMed:16673149" FT /id="VAR_071930" FT VARIANT 2562 FT /note="S -> G (in dbSNP:rs41310927)" FT /evidence="ECO:0000269|PubMed:14574646" FT /id="VAR_019084" FT VARIANT 2620 FT /note="Q -> H (in dbSNP:rs12138336)" FT /id="VAR_046761" FT VARIANT 2647 FT /note="L -> I (in dbSNP:rs3762271)" FT /evidence="ECO:0000269|PubMed:14574646, FT ECO:0000269|PubMed:16673149, ECO:0000269|PubMed:18204051" FT /id="VAR_019085" FT VARIANT 3132 FT /note="L -> R (in dbSNP:rs36004306)" FT /evidence="ECO:0000269|PubMed:14574646" FT /id="VAR_019086" FT VARIANT 3180 FT /note="Q -> P (in dbSNP:rs193251130)" FT /evidence="ECO:0000269|PubMed:16673149, FT ECO:0000269|PubMed:27535533" FT /id="VAR_071931" FT VARIANT 3258 FT /note="H -> R (in dbSNP:rs7528827)" FT /id="VAR_046762" FT CONFLICT 2355 FT /note="Q -> R (in Ref. 1; AAN40011 and 2; AAR12641)" FT /evidence="ECO:0000305" FT CONFLICT 2977 FT /note="I -> V (in Ref. 7; BAA91676)" FT /evidence="ECO:0000305" FT CONFLICT 3049 FT /note="F -> S (in Ref. 7; BAA91676)" FT /evidence="ECO:0000305" SQ SEQUENCE 3477 AA; 409800 MW; EB6EDAD3FF186108 CRC64; MANRRVGRGC WEVSPTERRP PAGLRGPAAE EEASSPPVLS LSHFCRSPFL CFGDVLLGAS RTLSLALDNP NEEVAEVKIS HFPAADLGFS VSQRCFVLQP KEKIVISVNW TPLKEGRVRE IMTFLVNDVL KHQAILLGNA EEQKKKKRSL WDTIKKKKIS ASTSHNRRVS NIQNVNKTFS VSQKVDRVRS PLQACENLAM NEGGPPTENN SLILEENKIP ISPISPAFNE CHGATCLPLS VRRSTTYSSL HASENRELLN VHSANVSKVS FNEKAVTETS FNSVNVNGQR GENSKLSLTP NCSSTLNITQ SQIHFLSPDS FVNNSHGANN ELELVTCLSS DMFMKDNSQP VHLESTIAHE IYQKILSPDS FIKDNYGLNQ DLESESVNPI LSPNQFLKDN MAYMCTSQQT CKVPLSNENS QVPQSPEDWR KSEVSPRIPE CQGSKSPKAI FEELVEMKSN YYSFIKQNNP KFSAVQDISS HSHNKQPKRR PILSATVTKR KATCTRENQT EINKPKAKRC LNSAVGEHEK VINNQKEKED FHSYLPIIDP ILSKSKSYKN EVTPSSTTAS VARKRKSDGS MEDANVRVAI TEHTEVREIK RIHFSPSEPK TSAVKKTKNV TTPISKRISN REKLNLKKKT DLSIFRTPIS KTNKRTKPII AVAQSSLTFI KPLKTDIPRH PMPFAAKNMF YDERWKEKQE QGFTWWLNFI LTPDDFTVKT NISEVNAATL LLGIENQHKI SVPRAPTKEE MSLRAYTARC RLNRLRRAAC RLFTSEKMVK AIKKLEIEIE ARRLIVRKDR HLWKDVGERQ KVLNWLLSYN PLWLRIGLET TYGELISLED NSDVTGLAMF ILNRLLWNPD IAAEYRHPTV PHLYRDGHEE ALSKFTLKKL LLLVCFLDYA KISRLIDHDP CLFCKDAEFK ASKEILLAFS RDFLSGEGDL SRHLGLLGLP VNHVQTPFDE FDFAVTNLAV DLQCGVRLVR TMELLTQNWD LSKKLRIPAI SRLQKMHNVD IVLQVLKSRG IELSDEHGNT ILSKDIVDRH REKTLRLLWK IAFAFQVDIS LNLDQLKEEI AFLKHTKSIK KTISLLSCHS DDLINKKKGK RDSGSFEQYS ENIKLLMDWV NAVCAFYNKK VENFTVSFSD GRVLCYLIHH YHPCYVPFDA ICQRTTQTVE CTQTGSVVLN SSSESDDSSL DMSLKAFDHE NTSELYKELL ENEKKNFHLV RSAVRDLGGI PAMINHSDMS NTIPDEKVVI TYLSFLCARL LDLRKEIRAA RLIQTTWRKY KLKTDLKRHQ EREKAARIIQ LAVINFLAKQ RLRKRVNAAL VIQKYWRRVL AQRKLLMLKK EKLEKVQNKA ASLIQGYWRR YSTRQRFLKL KYYSIILQSR IRMIIAVTSY KRYLWATVTI QRHWRAYLRR KQDQQRYEML KSSTLIIQSM FRKWKQRKMQ SQVKATVILQ RAFREWHLRK QAKEENSAII IQSWYRMHKE LRKYIYIRSC VVIIQKRFRC FQAQKLYKRR KESILTIQKY YKAYLKGKIE RTNYLQKRAA AIQLQAAFRR LKAHNLCRQI RAACVIQSYW RMRQDRVRFL NLKKTIIKFQ AHVRKHQQRQ KYKKMKKAAV IIQTHFRAYI FAMKVLASYQ KTRSAVIVLQ SAYRGMQARK MYIHILTSVI KIQSYYRAYV SKKEFLSLKN ATIKLQSTVK MKQTRKQYLH LRAAALFIQQ CYRSKKIAAQ KREEYMQMRE SCIKLQAFVR GYLVRKQMRL QRKAVISLQS YFRMRKARQY YLKMYKAIIV IQNYYHAYKA QVNQRKNFLQ VKKAATCLQA AYRGYKVRQL IKQQSIAALK IQSAFRGYNK RVKYQSVLQS IIKIQRWYRA YKTLHDTRTH FLKTKAAVIS LQSAYRGWKV RKQIRREHQA ALKIQSAFRM AKAQKQFRLF KTAALVIQQN FRAWTAGRKQ CMEYIELRHA VLVLQSMWKG KTLRRQLQRQ HKCAIIIQSY YRMHVQQKKW KIMKKAALLI QKYYRAYSIG REQNHLYLKT KAAVVTLQSA YRGMKVRKRI KDCNKAAVTI QSKYRAYKTK KKYATYRASA IIIQRWYRGI KITNHQHKEY LNLKKTAIKI QSVYRGIRVR RHIQHMHRAA TFIKAMFKMH QSRISYHTMR KAAIVIQVRC RAYYQGKMQR EKYLTILKAV KVLQASFRGV RVRRTLRKMQ TAATLIQSNY RRYRQQTYFN KLKKITKTVQ QRYWAMKERN IQFQRYNKLR HSVIYIQAIF RGKKARRHLK MMHIAATLIQ RRFRTLMMRR RFLSLKKTAI LIQRKYRAHL CTKHHLQFLQ VQNAVIKIQS SYRRWMIRKR MREMHRAATF IQSTFRMHRL HMRYQALKQA SVVIQQQYQA NRAAKLQRQH YLRQRHSAVI LQAAFRGMKT RRHLKSMHSS ATLIQSRFRS LLVRRRFISL KKATIFVQRK YRATICAKHK LYQFLHLRKA AITIQSSYRR LMVKKKLQEM QRAAVLIQAT FRMYRTYITF QTWKHASILI QQHYRTYRAA KLQRENYIRQ WHSAVVIQAA YKGMKARQLL REKHKASIVI QSTYRMYRQY CFYQKLQWAT KIIQEKYRAN KKKQKVFQHN ELKKETCVQA GFQDMNIKKQ IQEQHQAAII IQKHCKAFKI RKHYLHLRAT VVSIQRRYRK LTAVRTQAVI CIQSYYRGFK VRKDIQNMHR AATLIQSFYR MHRAKVDYET KKTAIVVIQN YYRLYVRVKT ERKNFLAVQK SVRTIQAAFR GMKVRQKLKN VSEEKMAAIV NQSALCCYRS KTQYEAVQSE GVMIQEWYKA SGLACSQEAE YHSQSRAAVT IQKAFCRMVT RKLETQKCAA LRIQFFLQMA VYRRRFVQQK RAAITLQHYF RTWQTRKQFL LYRKAAVVLQ NHYRAFLSAK HQRQVYLQIR SSVIIIQARS KGFIQKRKFQ EIKNSTIKIQ AMWRRYRAKK YLCKVKAACK IQAWYRCWRA HKEYLAILKA VKIIQGCFYT KLERTRFLNV RASAIIIQRK WRAILPAKIA HEHFLMIKRH RAACLIQAHY RGYKGRQVFL RQKSAALIIQ KYIRAREAGK HERIKYIEFK KSTVILQALV RGWLVRKRFL EQRAKIRLLH FTAAAYYHLN AVRIQRAYKL YLAVKNANKQ VNSVICIQRW FRARLQEKRF IQKYHSIKKI EHEGQECLSQ RNRAASVIQK AVRHFLLRKK QEKFTSGIIK IQALWRGYSW RKKNDCTKIK AIRLSLQVVN REIREENKLY KRTALALHYL LTYKHLSAIL EALKHLEVVT RLSPLCCENM AQSGAISKIF VLIRSCNRSI PCMEVIRYAV QVLLNVSKYE KTTSAVYDVE NCIDILLELL QIYREKPGNK VADKGGSIFT KTCCLLAILL KTTNRASDVR SRSKVVDRIY SLYKLTAHKH KMNTERILYK QKKNSSISIP FIPETPVRTR IVSRLKPDWV LRRDNMEEIT NPLQAIQMVM DTLGIPY //