KNL1
entrez
57082
canonical
uniprot
Q8NG31
canonical
ensembl
ENSG00000137812
resolver
ensp
ENSP00000335463
resolver
ensp
ENSP00000382576
resolver
genesymbol
KNL1
resolver
genesymbol_syn
CASC5
resolver
genesymbol_syn
KIAA1570
resolver
hgnc
HGNC:24054
resolver
uniprot
Q8NHE1
resolver
uniprot
Q8WXA6
resolver
uniprot
Q9HCK2
resolver
uniprot
Q9NR92
resolver
uniprot_entry
KNL1_HUMAN
resolver
uniprot_sec
Q8NHE1
resolver
uniprot_sec
Q8WXA6
resolver
uniprot_sec
Q9HCK2
resolver
uniprot_sec
Q9NR92
resolver
amino_acid_sequence
MDGVSSEANEENDNIERPVRRRHSSILKPPRSPLQDLRGGNERVQESNALRNKKNSRRVSFADTIKVFQTESHMKIVRKSEMEGCSAMVPSQLQLLPPGFKRFSCLSLPETETGENLLLIQNKKLEDNYCEITGMNTLLSAPIHTQMQQKEFSIIEHTRERKHANDQTVIFSDENQMDLTSSHTVMITKGLLDNPISEKSTKIDTTSFLANLKLHTEDSRMKKEVNFSVDQNTSSENKIDFNDFIKRLKTGKCSAFPDVPDKENFEIPIYSKEPNSASSTHQMHVSLKEDENNSNITRLFREKDDGMNFTQCHTANIQTLIPTSSETNSRESKGNDITIYGNDFMDLTFNHTLQILPATGNFSEIENQTQNAMDVTTGYGTKASGNKTVFKSKQNTAFQDLSINSADKIHITRSHIMGAETHIVSQTCNQDARILAMTPESIYSNPSIQGCKTVFYSSCNDAMEMTKCLSNMREEKNLLKHDSNYAKMYCNPDAMSSLTEKTIYSGEENMDITKSHTVAIDNQIFKQDQSNVQIAAAPTPEKEMMLQNLMTTSEDGKMNVNCNSVPHVSKERIQQSLSNPLSISLTDRKTELLSGENMDLTESHTSNLGSQVPLAAYNLAPESTSESHSQSKSSSDECEEITKSRNEPFQRSDIIAKNSLTDTWNKDKDWVLKILPYLDKDSPQSADCNQEIATSHNIVYCGGVLDKQITNRNTVSWEQSLFSTTKPLFSSGQFSMKNHDTAISSHTVKSVLGQNSKLAEPLRKSLSNPTPDYCHDKMIICSEEEQNMDLTKSHTVVIGFGPSELQELGKTNLEHTTGQLTTMNRQIAVKVEKCGKSPIEKSGVLKSNCIMDVLEDESVQKPKFPKEKQNVKIWGRKSVGGPKIDKTIVFSEDDKNDMDITKSYTIEINHRPLLEKRDCHLVPLAGTSETILYTCRQDDMEITRSHTTALECKTVSPDEITTRPMDKTVVFVDNHVELEMTESHTVFIDYQEKERTDRPNFELSQRKSLGTPTVICTPTEESVFFPGNGESDRLVANDSQLTPLEEWSNNRGPVEVADNMELSKSATCKNIKDVQSPGFLNEPLSSKSQRRKSLKLKNDKTIVFSENHKNDMDITQSCMVEIDNESALEDKEDFHLAGASKTILYSCGQDDMEITRSHTTALECKTLLPNEIAIRPMDKTVLFTDNYSDLEVTDSHTVFIDCQATEKILEENPKFGIGKGKNLGVSFPKDNSCVQEIAEKQALAVGNKIVLHTEQKQQLFAATNRTTNEIIKFHSAAMDEKVIGKVVDQACTLEKAQVESCQLNNRDRRNVDFTSSHATAVCGSSDNYSCLPNVISCTDNLEGSAMLLCDKDEEKANYCPVQNDLAYANDFASEYYLESEGQPLSAPCPLLEKEEVIQTSTKGQLDCVITLHKDQDLIKDPRNLLANQTLVYSQDLGEMTKLNSKRVSFKLPKDQMKVYVDDIYVIPQPHFSTDQPPLPKKGQSSINKEEVILSKAGNKSLNIIENSSAPICENKPKILNSEEWFAAACKKELKENIQTTNYNTALDFHSNSDVTKQVIQTHVNAGEAPDPVITSNVPCFHSIKPNLNNLNGKTGEFLAFQTVHLPPLPEQLLELGNKAHNDMHIVQATEIHNINIISSNAKDSRDEENKKSHNGAETTSLPPKTVFKDKVRRCSLGIFLPRLPNKRNCSVTGIDDLEQIPADTTDINHLETQPVSSKDSGIGSVAGKLNLSPSQYINEENLPVYPDEINSSDSINIETEEKALIETYQKEISPYENKMGKTCNSQKRTWVQEEEDIHKEKKIRKNEIKFSDTTQDREIFDHHTEEDIDKSANSVLIKNLSRTPSSCSSSLDSIKADGTSLDFSTYRSSQMESQFLRDTICEESLREKLQDGRITIREFFILLQVHILIQKPRQSNLPGNFTVNTPPTPEDLMLSQYVYRPKIQIYREDCEARRQKIEELKLSASNQDKLLVDINKNLWEKMRHCSDKELKAFGIYLNKIKSCFTKMTKVFTHQGKVALYGKLVQSAQNEREKLQIKIDEMDKILKKIDNCLTEMETETKNLEDEEKNNPVEEWDSEMRAAEKELEQLKTEEEELQRNLLELEVQKEQTLAQIDFMQKQRNRTEELLDQLSLSEWDVVEWSDDQAVFTFVYDTIQLTITFEESVVGFPFLDKRYRKIVDVNFQSLLDEDQAPPSSLLVHKLIFQYVEEKESWKKTCTTQHQLPKMLEEFSLVVHHCRLLGEEIEYLKRWGPNYNLMNIDINNNELRLLFSSSAAFAKFEITLFLSAYYPSVPLPSTIQNHVGNTSQDDIATILSKVPLENNYLKNVVKQIYQDLFQDCHFYH
uniprot
proteins
disease_involvement
DISEASE: Note=A chromosomal aberration involving KNL1 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A. May give rise to a KMT2A-KNL1 fusion protein. {ECO:0000269|PubMed:12618766}.; DISEASE: Microcephaly 4, primary, autosomal recessive (MCPH4) [MIM:604321]: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals have mild to moderate intellectual disability. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. {ECO:0000269|PubMed:22983954, ECO:0000269|PubMed:26626498, ECO:0000269|PubMed:27149178, ECO:0000269|PubMed:37937525}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15502821, PubMed:17981135, PubMed:18045986, PubMed:19893618, PubMed:21199919, PubMed:22000412, PubMed:22331848, PubMed:27881301, PubMed:30100357). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:18045986, PubMed:19893618, PubMed:27881301). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:38459127, PubMed:38459128). Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors (PubMed:19893618). Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore (PubMed:18045986, PubMed:27881301). Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1 (PubMed:30100357). Recruits MAD2L1 to the kinetochore and also directly links BUB1 and BUB1B to the kinetochore (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:22331848, PubMed:25308863). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986, ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:21199919, ECO:0000269|PubMed:22000412, ECO:0000269|PubMed:22331848, ECO:0000269|PubMed:25308863, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:30100357, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}.
uniprot
proteins
mass_dalton
265391
uniprot
proteins
mutagenesis
MUTAGEN 24..25; /note="SS->DD: Decreases interaction with PPP1CA and abolishes binding to microtubules."; /evidence="ECO:0000269|PubMed:30100357"; MUTAGEN 25..28; /note="SILK->AAAA: Decreases interaction with PPP1CA."; /evidence="ECO:0000269|PubMed:30100357"; MUTAGEN 60; /note="S->D: Decreases interaction with PPP1CA."; /evidence="ECO:0000269|PubMed:30100357
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by AURKB negatively regulates its interaction with protein phosphatase 1 (PP1) subunit PPP1CA and with microtubules. {ECO:0000269|PubMed:30100357}.
uniprot
proteins
pubmed
10980622
uniprot
proteins
pubmed
10997877
uniprot
proteins
pubmed
12087463
uniprot
proteins
pubmed
12618766
uniprot
proteins
pubmed
12618768
uniprot
proteins
pubmed
15502821
uniprot
proteins
pubmed
15579588
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
17981135
uniprot
proteins
pubmed
18045986
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18987736
uniprot
proteins
pubmed
19450515
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19893618
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20231385
uniprot
proteins
pubmed
20819937
uniprot
proteins
pubmed
21199919
uniprot
proteins
pubmed
22000412
uniprot
proteins
pubmed
22201036
uniprot
proteins
pubmed
22331848
uniprot
proteins
pubmed
22660415
uniprot
proteins
pubmed
22983954
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24530301
uniprot
proteins
pubmed
25308863
uniprot
proteins
pubmed
26345214
uniprot
proteins
pubmed
26621532
uniprot
proteins
pubmed
26626498
uniprot
proteins
pubmed
27149178
uniprot
proteins
pubmed
27697923
uniprot
proteins
pubmed
27881301
uniprot
proteins
pubmed
28441529
uniprot
proteins
pubmed
30100357
uniprot
proteins
pubmed
37937525
uniprot
proteins
pubmed
38459127
uniprot
proteins
pubmed
38459128
uniprot
proteins
sequence_length
2342
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:38459128}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:20819937, ECO:0000269|PubMed:22660415, ECO:0000269|PubMed:26345214, ECO:0000269|PubMed:26621532, ECO:0000269|PubMed:38459128}. Cytoplasm {ECO:0000250|UniProtKB:Q66JQ7}. Note=Weakly expressed in interphase nuclei. Expression increases from prophase to late anaphase, but greatly diminishes from the telophase and cytokinesis to early G1 phase of cell cycle (PubMed:19893618). Localizes to the cytoplasm during meiotic prophase I and then the nucleus as meiosis progresses (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:19893618}.
uniprot
proteins