Conserved Protein Domain Family
AAA_6

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pfam12774: AAA_6 
Hydrolytic ATP binding site of dynein motor region
This domain is found in human cytoplasmic dynein-2 proteins. Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies. Dyneins share a conserved motor domain that couples cycles of ATP hydrolysis with conformational changes to produce movement. Structural analysis reveal that the motor's ring consists of six AAA+ domains (ATPases associated with various cellular activities: AAA1-AAA6). This is the first site (out of four nucleotide binding sites in the dynein motor) where the movement depends on ATP hydrolysis. When this site is nucleotide free or bound to ADP, the microtubule binding domain (MTBD) binds to the microtubule and the linker adopts the straight post-power-stroke conformation. Upon ATP binding and hydrolysis, the MTBD detaches from the microtubule and the linker is primed into the pre-power-stroke conformation. Dynein's AAA+ domains are each divided into an alpha/beta large subdomain designated with an L and and alpha small subdomains designated with an S. This is the AAA1 large (AAA1L) subdomain with the accompanying small subdomain (AAA1S). AAA1L, AAA1S and AAA2L enclose ADP.vanadate (ADP.Vi, ATP-hydrolysis transition state analogue). The AAA1L sensor-I loop, which varies in position depending on dynein's nucleotide state, swings in to contact AAA2L forming the important AAA1 nucleotide-binding site.
Statistics
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PSSM-Id: 463697
Aligned: 80 rows
Threshold Bit Score: 414.957
Created: 24-Mar-2022
Updated: 17-Oct-2022
Structure
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Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
XP_001328084 1450 YGYEYQGNAPKLVHTPLTDICWSTLCEGMHLGFAGNPYGPAGTGKTESVKALGQAMGRQVLVFNCGDGIDVKSICRIFTG 1529
KOX75896     1112 YGYEYSYHKQHLVNTPLTNRCFHTLMQAYEYHLYGAITGPSATGKSETIKSLAKAFAVQFRSFNCINTLSYNFVTQIFKG 1191
EZA60901      870 YGYEYNFYQQNIVNTPLTDRCFRTILQAYRYHLYGSITGPTDTGKTETVRNLTMALAKPFYVINCDNSISYDCILKTFKG 949 
EFN82623      997 YGYEYSHYQQVVINTPLTDRCFRAVMQAYRYHLFSIIIGPTGAGKTEAIKSLTSTLAKPFYLVSCSHDVSYEYVAQTLKG 1076
KYQ58466     1125 YEYEYNCCQQNIVNTPLTDRCFRTILQAYRYHLYSSIIGPTGTGKTETIKSLTRAIAKPYYVINCNNSISYECVIRTFKG 1204
CAP30931     2185 YTYEYQGNYAKLVHTPLTDKCYLTLTQAMYMGLGGNPYGPAGTGKTESVKALAALMGRQVLVFNCDEGIDVTSMGRIFTG 2264
KNE55585     1413 YSFEYQGNPSKLVQTPLTDTCFATLMQAMSEGLGGCLYGPAGTGKTESVKSLGYLLGRQVLVFNCDEALDVSSITRLFCG 1492
XP_017990903 1792 YGFEVLGAQERLIPTPLTNASYITLTQALKARQGGAPFGPAGTGKTETVKALGAELGRWVLVFNCDQQFDESAMARLLLG 1871
XP_003683813 1758 YSYSYIGVPENLIRTESLLTAYVSLMHAFDQNYGSSLFGPAATGKTETTKSLGHSLGKTVVIFNCDDSFDIDSLTRIMGG 1837
EFC48313     1846 YGFEYLGVIEKLVQTPLTDKCYLALTQALHSRFGGSPFGPAGTGKTETVKALGAQLGRFVLVFNCDETFDFKAMGRIFLG 1925
XP_001328084 1530 LVQCGAWGCFDEFNRLDELVLSAVSQQIQAIQTAILKKKENVALLGKTIP-LDLKSGIFVTLNPagkAYGGRSKLPNNLK 1608
KOX75896     1192 FISCGAWLCFVNFNTLKIDFLSRLAQILTSVFYIIATNLKITMFEGSSLR-INQIGHICIITKL---SLFKCPNIPDNLK 1267
EZA60901      950 VVSCGAWICFKNFNKLKLELLSAIAQNLTQMMQAVSSNLKTVSFEGCNLD-LDASGNICINISL---EQSKHTDLPDNLK 1025
EFN82623     1077 AVSCGAWICLENFDGLKLELLSAIAQNLSQMKQAVSSRLKTVNLDGCVLN-LNASGNVCVNINS---ERSRHSNLPGNLK 1152
KYQ58466     1205 VISCGAWICFENFNRLKLELLSSIAQNLIQMKQAVSSKLKIISFEGCDLN-LNVSGNICVNINS---EQSGYADLPDNLK 1280
CAP30931     2265 IVECGAWGCFDEFNRLDSTVLSAVSMQIQTIQGAIKSRAGSCTFGGKNVQ-VNPNSAIFVTLNPagkGYGGRQKMPDNLK 2343
KNE55585     1493 IVKCGAWGCFDEFNRLSAGVLAAVSNLVSTIQQALLKRFPTVQIAGTELT-VNHSSCLFVTLNPagkQYKGRQQLPNNLK 1571
XP_017990903 1872 LARVGAWGCFDEFNRLDERVLSSVSQSMQAVQQALAHETEA-RI-GSVLTrVQPSTGLFVTMNP---SYAGRSHLPDNLV 1946
XP_003683813 1838 ICQLGVWCCFDEFNRLPKAILSAVASYLEAIQFSLTRSLNSVQLRQSSFK-LHKDSRFIVTLNP---TYEGRSELPTNLK 1913
EFC48313     1926 LCQCGSWGCFDEFNRLNEKMMSAVSQQIQTIQIALRDRKTSIELIGRQCS-VHDNTGIFITMNP---GYAGRSNLPDNLK 2001
XP_001328084 1609 ALFRSVSMSAPDKALIGEIMLYSEGFQASTELAQRLTTTFSLADQLL-SKQRHYDWGLRAQKTVLNMAGQWLRE--SDGs 1685
KOX75896     1268 ILFRTVTMIVPDMNKIVEVEFFAGGMSNSKLLTSKLVSLYKILSEQL-WCQSCNIFNLYSMKTIVKTTIYLKRS--FPD- 1343
EZA60901     1026 VLFRSVSMIAPDIYKIVEVGLFAGGFLHAKDLAAKLVVSYKLLTDHLrGKHYFYNLGASSLKTVIAAATSMKRN--IPN- 1102
EFN82623     1153 VLFRPVAMMVPDVGRIAEVVLFAGGFLHAKDLAMKLTLTYKLLSEHL-EEKNCYNLGLSSLKTVIETAISMKRN--LSE- 1228
KYQ58466     1281 ILFRSVSMISPDIGKIAEIELFAGGFNHAKNLATKLAVSYKLLSEHM-GDKRHYNFSMSSLKTVVETAINMKRN--IPN- 1356
CAP30931     2344 QLFRAVVMGKPDNELISSTILYSEGFVDATSLARKIVSVFQLSRQML-SKQQHYDWGLRALKVVLGGCGALRRA--QPN- 2419
KNE55585     1572 QLFRNIAMTHPDVTYICQIELKAQGFDNTDDLGKVVVEFYDACRKIL-SVQSHYDWGLRALKAVLMTAGSLRRs-aGQG- 1648
XP_017990903 1947 KLFRRVAMTQPDSTLIVEGWLRMHGFTDASSLACKMVTLFQLCMEQL-SDAPHYDFGLRALKAVLVGAAHARRS--NPA- 2022
XP_003683813 1914 KLFRSFSMSHADLYTISSVYLEMMGYPDWSDLSKTLSNLMLELDKQC-TKQLHYDFGLRCLKTILRNAQILKKKdvHSR- 1991
EFC48313     2002 QLFRNIAMVKPDKELIAQVILYSQGFKLAEELSKKVVLFFDLCRDKL-SHQSHYDFGLRALKSVLVNAGYLKRNfsSTN- 2079
XP_001328084 1686 QNEADIVIRALLFDTLGKLDDKDRSLFLDIVKDIFKTQdaNANN--EN--SLQDTINEIIKEKK-LQPSQQQLTKIALLH 1760
KOX75896     1344 QNEIVLLLRSLIDVNLPKLCNIDTHIFRNIVHDMFPNV--TLLP--SDytVFLETLETVCTSKSiYI-HDIFKLKIIQIF 1418
EZA60901     1103 ENEYTLLLRSMIDVNIPQLCNTDVPIFQSIIRNVFPEP--SMPP--FDcsTILNALEKVCAKRF-LTLHSVFKLKVIQII 1177
EFN82623     1229 ENEYTLLLRSIIDINIPQLCNTDVIIFQDIMQDVFPEs-vMLP---FDhsAISSALEDVCAKRR-LTLHNIFKLKAIQTI 1303
KYQ58466     1357 ENEYTLLLRSMIHINIPQLCNTDISIFQNIMQDIFPES--DVLP--FDcsAILNALEIVCTKRL-LTLHTVFKLKAIQII 1431
CAP30931     2420 KNETDLVVQALLLNTLSKLTFSDSERFNSLIDDIFANV----TKemTKfeELVEPLGVAAKEIG-ISLGEKQMEKVFQLY 2494
KNE55585     1649 VSGSDVLAEAMRVSTESKLTGPDKQVFLGLLSLYFGS---EGNR--STtgDFVRAMADAYKQLG-LTPLDWQIQAGFQLH 1722
XP_017990903 2023 ESEINVIVQSVQETVPPRLVAEDAPLFAELVADVFPGI----APssSMskDLVQALEAECEAQH-LG-TGAWLEKIWQLH 2096
XP_003683813 1992 LK---VLLNSIIQVISPKLNMDDTVLLHHLIRKYFNV---DLPH--IDndMFISTLVNQM--PYkYS-A-HFIQLCKHLY 2059
EFC48313     2080 I-ESKHLIQSIQDTIIPKLVGDDVSQLKFLISNLFPGL--ETVS--NPltELRQYIFEICNLYSyLA-DERWVEKIVQLY 2153
XP_001328084 1761 QLLQHRTGAVIVGPAGCGKS 1780
KOX75896     1419 ELMHIHQCLILVGDPFVGKT 1438
EZA60901     1178 ELTYVRRGLILIGNPLAGKT 1197
EFN82623     1304 ELMYVHRALVLVGEPLSGKT 1323
KYQ58466     1432 ELMNVHRGLILISNSLGGKT 1451
CAP30931     2495 EQMRQRIGVVVVGAAGSGKS 2514
KNE55585     1723 TSCAQRMGVCIVGLPRSGKV 1742
XP_017990903 2097 HVLDIAPGVVLVGEAGTGKT 2116
XP_003683813 2060 ELQGINQSVIIMGKTGSGKS 2079
EFC48313     2154 NIQNLHHGFICVGPAASGKS 2173
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