forkhead associated (FHA) domain found in kinesin-like protein KIF1A; KIF1A, also called axonal transporter of synaptic vesicles (ATSV), microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein, or Unc-104, is an axonal transporter of synaptic vesicles, which is mutated in hereditary sensory and autonomic neuropathy type 2. It is also required for neuronal dense core vesicle (DCV) transport to dendritic spines and axons. The calcium-dependent interaction with CALM1 increases vesicle motility, and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  165 TPHLVNLNEDPLMSECLLYYIKDGITRVGREDGERRQDIVLSGHFIKEEHCVFRSDSRGGSEAVVTLEPCEGADTYVNGK 244
Cdd:cd22726      1 TPHLVNLNEDPLMSECLLYYIKDGITRVGREDAERRQDIVLSGHFIKEEHCIFRSDTRSGGEAVVTLEPCEGADTYVNGK 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2462574518  245 KVTEPSILRSGNRIIMGKSHVFRFNHPEQARQERE 279
Cdd:cd22726     81 KVTEPSILRSGNRIIMGKSHVFRFNHPEQARQERE 115

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518 1344 RVSPIVSKKGYLHFLEPHTSGWARRFVVVRRPYAYMYNSDKDTVERFVLNLATAQVEYSEDQQAMLKTPNTFAVCTEHRG 1423
Cdd:cd01233      1 PKSPVVSKRGYLLFLEDATDGWVRRWVVLRRPYLHIYSSEKDGDERGVINLSTARVEYSPDQEALLGRPNVFAVYTPTNS 80

                           90       100
                   ....*....|....*....|...
gi 2462574518 1424 ILLQAASDKDMHDWLYAFNPLLA 1446
Cdd:cd01233     81 YLLQARSEKEMQDWLYAIDPLLA 103

Kinesin protein 1B; This domain family is found in eukaryotes, and is approximately 50 amino acids in length. The family is found in association with pfam00225, pfam00498. KIF1B is an anterograde motor for transport of mitochondria in axons of neuronal cells.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2462574518  479 LRQRLDLMREMYDRAAEVPSSVIEDCDNvvtggDPFYDRFPWFRLVGS 526
Cdd:pfam12423    1 LENRLVDMREMYQEYKEGEYSQHFEVDR-----DPFYEPPENHNLIGV 43

forkhead associated (FHA) domain found in kinesin-like protein KIF1A; KIF1A, also called axonal transporter of synaptic vesicles (ATSV), microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein, or Unc-104, is an axonal transporter of synaptic vesicles, which is mutated in hereditary sensory and autonomic neuropathy type 2. It is also required for neuronal dense core vesicle (DCV) transport to dendritic spines and axons. The calcium-dependent interaction with CALM1 increases vesicle motility, and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  165 TPHLVNLNEDPLMSECLLYYIKDGITRVGREDGERRQDIVLSGHFIKEEHCVFRSDSRGGSEAVVTLEPCEGADTYVNGK 244
Cdd:cd22726      1 TPHLVNLNEDPLMSECLLYYIKDGITRVGREDAERRQDIVLSGHFIKEEHCIFRSDTRSGGEAVVTLEPCEGADTYVNGK 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2462574518  245 KVTEPSILRSGNRIIMGKSHVFRFNHPEQARQERE 279
Cdd:cd22726     81 KVTEPSILRSGNRIIMGKSHVFRFNHPEQARQERE 115

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518 1344 RVSPIVSKKGYLHFLEPHTSGWARRFVVVRRPYAYMYNSDKDTVERFVLNLATAQVEYSEDQQAMLKTPNTFAVCTEHRG 1423
Cdd:cd01233      1 PKSPVVSKRGYLLFLEDATDGWVRRWVVLRRPYLHIYSSEKDGDERGVINLSTARVEYSPDQEALLGRPNVFAVYTPTNS 80

                           90       100
                   ....*....|....*....|...
gi 2462574518 1424 ILLQAASDKDMHDWLYAFNPLLA 1446
Cdd:cd01233     81 YLLQARSEKEMQDWLYAIDPLLA 103

Kinesin protein 1B; This domain family is found in eukaryotes, and is approximately 50 amino acids in length. The family is found in association with pfam00225, pfam00498. KIF1B is an anterograde motor for transport of mitochondria in axons of neuronal cells.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2462574518  479 LRQRLDLMREMYDRAAEVPSSVIEDCDNvvtggDPFYDRFPWFRLVGS 526
Cdd:pfam12423    1 LENRLVDMREMYQEYKEGEYSQHFEVDR-----DPFYEPPENHNLIGV 43

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518 1349 VSKKGYLHFLEPH-TSGWARRFVVVRRPYAYMYNSD---KDTVERFVLNLATAQVEYSEDQqAMLKTPNTFAVCT----E 1420
Cdd:pfam00169    1 VVKEGWLLKKGGGkKKSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVAS-DSPKRKFCFELRTgertG 79

                           90       100
                   ....*....|....*....|..
gi 2462574518 1421 HRGILLQAASDKDMHDWLYAFN 1442
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAIQ 101

Kinesin motor domain;

                           10        20
                   ....*....|....*....|....*...
gi 2462574518    1 MVAALSPADINYDETLSTLRYADRAKQI 28
Cdd:pfam00225  299 MIANISPSSSNYEETLSTLRFASRAKNI 326

Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  185 IKDGITRVGREDGerrQDIVLSGHFIKEEHCVFRSDSRGgseavVTLEpcegaD------TYVNGKKVTEPSILRSGNRI 258
Cdd:COG1716     18 LDGGPLTIGRAPD---NDIVLDDPTVSRRHARIRRDGGG-----WVLE-----DlgstngTFVNGQRVTEPAPLRDGDVI 84

                           90
                   ....*....|
gi 2462574518  259 IMGKsHVFRF 268
Cdd:COG1716     85 RLGK-TELRF 93

Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462574518   190 TRVGRedGERRQDIVLSGHFIKEEHCVFRSDSRGgseaVVTLEPC-EGADTYVNGKKV 246
Cdd:smart00240    1 VTIGR--SSEDCDIQLDGPSISRRHAVIVYDGGG----RFYLIDLgSTNGTFVNGKRI 52

forkhead associated (FHA) domain found in kinesin-like protein KIF1A; KIF1A, also called axonal transporter of synaptic vesicles (ATSV), microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein, or Unc-104, is an axonal transporter of synaptic vesicles, which is mutated in hereditary sensory and autonomic neuropathy type 2. It is also required for neuronal dense core vesicle (DCV) transport to dendritic spines and axons. The calcium-dependent interaction with CALM1 increases vesicle motility, and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  165 TPHLVNLNEDPLMSECLLYYIKDGITRVGREDGERRQDIVLSGHFIKEEHCVFRSDSRGGSEAVVTLEPCEGADTYVNGK 244
Cdd:cd22726      1 TPHLVNLNEDPLMSECLLYYIKDGITRVGREDAERRQDIVLSGHFIKEEHCIFRSDTRSGGEAVVTLEPCEGADTYVNGK 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2462574518  245 KVTEPSILRSGNRIIMGKSHVFRFNHPEQARQERE 279
Cdd:cd22726     81 KVTEPSILRSGNRIIMGKSHVFRFNHPEQARQERE 115

forkhead associated (FHA) domain found in the kinesin-like protein KIF1 family; The KIF1 family includes KIF1A, KIF1B, and KIF1C. KIF1A, also called axonal transporter of synaptic vesicles (ATSV), microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein, or Unc-104, is an axonal transporter of synaptic vesicles, which is mutated in hereditary sensory and autonomic neuropathy type 2. It is also required for neuronal dense core vesicle (DCV) transport to dendritic spines and axons. The calcium-dependent interaction with CALM1 increases vesicle motility, and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites. KIF1B, also called Klp, is a motor for anterograde transport of mitochondria. It has a microtubule plus end-directed motility. Isoform 1 mediates the transport of synaptic vesicles in neuronal cells, while isoform 2 is required for induction of neuronal apoptosis. KIF1C is a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum. It has a microtubule plus end-directed motility. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  165 TPHLVNLNEDPLMSECLLYYIKDGITRVGREDGERRQDIVLSGHFIKEEHCVFRSdsrggSEAVVTLEPCEGADTYVNGK 244
Cdd:cd22705      1 TPHLVNLNEDPLMSECLLYYIKPGITRVGRADADVPQDIQLSGTHILEEHCTFEN-----EDGVVTLEPCEGALTYVNGK 75

                           90       100
                   ....*....|....*....|....*.
gi 2462574518  245 KVTEPSILRSGNRIIMGKSHVFRFNH 270
Cdd:cd22705     76 RVTEPTRLKTGSRVILGKNHVFRFNH 101

Kinesin protein; This domain family is found in eukaryotes, and is typically between 131 and 151 amino acids in length. The family is found in association with pfam00225, pfam00498. There is a single completely conserved residue W that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  913 DYIPAVVDHRGGMPcMGTFLLHQGIQRRITVTLLHETGSHIRWKEVRELVVGRIRNTPETDESLIDPN--ILSLNILSSG 990
Cdd:pfam12473    1 EYVPVPVDQRSELD-PGTFQLHQGLQRRIVITLTHSSGDELPWERVRNVRVGDVRLLDMKGRVPDSDStpDVSLKLLSKP 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462574518  991 YIHPAQDDRqfldsdiprTFYQFEAAWDSSMHNSLLLNRVTPYREKIYMTLSAYIEMENCTQPAVVTKDFCMVFYSRDA 1069
Cdd:pfam12473   80 VVRFNADGT---------SSYTIEGQWDSSLHNSLLLNRVTADGYRVYLTLAWDVVSEKCAEPVRFSMDTAVQIYPRDE 149

forkhead associated (FHA) domain found in kinesin-like protein KIF14 and similar proteins; KIF14 is a microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity. It plays a role in many processes like cell division, cytokinesis and in cell proliferation and apoptosis. KIF14 is a potential oncogene and is involved in the metastasis of various cancers. Mutations of KIF14 cause primary microcephaly by impairing cytokinesis. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  164 KTPHLVNLNEDPLMSECLLYYIKDGITRVGREDGERRQDIVLSGHFIKEEHCVFRSdsrggSEAVVTLEPCEGADTYVNG 243
Cdd:cd22707      6 KLPNLVNLNEDPQLSEMLLYMLKEGQTRVGRSKASSSHDIQLSGALIADDHCTIEN-----NGGKVTIIPVGDAETYVNG 80

                           90       100
                   ....*....|....*....|....*...
gi 2462574518  244 KKVTEPSILRSGNRIIMGKSHVFRFNHP 271
Cdd:cd22707     81 ELISEPTVLHHGDRVILGGDHYFRFNHP 108

forkhead associated (FHA) domain found in kinesin-like protein KIF28P and similar proteins; KIF28P, also called kinesin-like protein 6 (KLP6), is a microtubule-dependent motor protein required for mitochondrion morphology and transport of mitochondria in neuronal cells. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  166 PHLVNLNEDPLMSECLLYYIKDGITRVGREDGERRQDIVLSGHFIKEEHCVFRSDSRGgseavVTLEPC-EGADTYVNGK 244
Cdd:cd22709      1 PHLLNLNEDPQLSGVIVHFLQEGETTIGRADAEPEPDIVLSGLSIQKQHAVITNTDGK-----VTIEPVsPGAKVIVNGV 75

                           90       100
                   ....*....|....*....|....*..
gi 2462574518  245 KVTEPSILRSGNRIIMGKSHVFRFNHP 271
Cdd:cd22709     76 PVTGETELHHLDRVILGSNHLYVFVGP 102

forkhead associated (FHA) domain found in the kinesin-like protein KIF13 family; The KIF13 family includes KIF13A and KIF13B. KIF13A, also called kinesin-like protein RBKIN, is a plus end-directed microtubule-dependent motor protein involved in intracellular transport and in regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis, and cytokinesis. It mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, KIF13A is required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. It is also required for the abscission step in cytokinesis: it mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis. KIF13B, also called kinesin-like protein GAKIN, is a novel kinesin-like protein that associates with the human homolog of the Drosophila discs large tumor suppressor in T lymphocytes. It is involved in reorganization of the cortical cytoskeleton. It regulates axon formation by promoting the formation of extra axons. KIF13B may be functionally important for the intracellular trafficking of membrane-associated guanylate kinase homologs (MAGUKs) and associated protein complexes. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  168 LVNLNEDPLMSECLLYYIKDgITRVGREDGERRQDIVLSGHFIKEEHCVFRSDSRGgseavVTLEPCEGADTYVNGKKVT 247
Cdd:cd22706      4 LVNLNADPSLNELLVYYLKE-HTLIGRSDAPTQQDIQLSGLGIQPEHCIITIENED-----VYLTPLEGARTCVNGSIVT 77

                           90       100
                   ....*....|....*....|....
gi 2462574518  248 EPSILRSGNRIIMGKSHVFRFNHP 271
Cdd:cd22706     78 EKTQLRHGDRILWGNNHFFRLNCP 101

forkhead associated (FHA) domain found in kinesin-like protein KIF13A; KIF13A, also called kinesin-like protein RBKIN, is a plus end-directed microtubule-dependent motor protein involved in intracellular transport and in regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis, and cytokinesis. It mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, KIF13A is required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. It is also required for the abscission step in cytokinesis: it mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  168 LVNLNEDPLMSECLLYYIKDGiTRVGredGERRQDIVLSGHFIKEEHCVFRSDSRGGseavVTLEPCEGADTYVNGKKVT 247
Cdd:cd22729      4 LVNLNADPALNELLVYYLKDH-TRVG---ADTSQDIQLFGIGIQPEHCVIDIAADGD----VTLTPKENARTCVNGTLVC 75

                           90       100       110
                   ....*....|....*....|....*....|.
gi 2462574518  248 EPSILRSGNRIIMGKSHVFRFNHPEQARQER 278
Cdd:cd22729     76 SVTQLWHGDRILWGNNHFFRINLPKRKRRDW 106

forkhead associated (FHA) domain found in afadin and similar proteins; Afadin, also called ALL1-fused gene from chromosome 6 protein, protein AF-6, Afadin adherens junction formation factor, or MLLT4, is a nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. It is essential for the organization of adherens junctions. It may play a key role in the organization of epithelial structures of the embryonic ectoderm. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  166 PHLVNLNEDPLMSECL-LYYIKDGITRVG--REDGERRQDIVLSGHFIKEEHCVFRSdsrggSEAVVTLEPCEG-ADTYV 241
Cdd:cd22711      2 PYLLELSPDGSDRDKPrRHRLQPNVTEVGseRSPANSGQFIQLFGPDILPRHCVITH-----MEGVVTVTPASQdAETYV 76

                           90       100       110
                   ....*....|....*....|....*....|
gi 2462574518  242 NGKKVTEPSILRSGNRIIMGKSHVFRFNHP 271
Cdd:cd22711     77 NGQRIYETTMLQHGMVVQFGRSHTFRFCDP 106

Kinesin motor domain, KIF1_like proteins; Kinesin motor domain, KIF1_like proteins. KIF1A (Unc104) transports synaptic vesicles to the nerve terminal, KIF1B has been implicated in transport of mitochondria. Both proteins are expressed in neurons. This catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases. Kinesins are microtubule-dependent molecular motors that play important roles in intracellular transport and in cell division. In most kinesins, the motor domain is found at the N-terminus (N-type). N-type kinesins are (+) end-directed motors, i.e. they transport cargo towards the (+) end of the microtubule. In contrast to the majority of dimeric kinesins, most KIF1A/Unc104 kinesins are monomeric motors. A lysine-rich loop in KIF1A binds to the negatively charged C-terminus of tubulin and compensates for the lack of a second motor domain, allowing KIF1A to move processively.

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 2462574518    1 MVAALSPADINYDETLSTLRYADRAKQIRCNAVIN 35
Cdd:cd01365    327 MIAAISPADINYEETLSTLRYADRAKKIVNRAVVN 361

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  1349 VSKKGYLHFLEP-HTSGWARRFVVVRRPYAYMYNSDK---DTVERFVLNLATAQVEYSEDQQAMlKTPNTFAVCTEHRG- 1423
Cdd:smart00233    1 VIKEGWLYKKSGgGKKSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSS-KKPHCFEIKTSDRKt 79

                            90
                    ....*....|....*....
gi 2462574518  1424 ILLQAASDKDMHDWLYAFN 1442
Cdd:smart00233   80 LLLQAESEEEREKWVEALR 98

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518 1349 VSKKGYLHFLEPH-TSGWARRFVVVRRPYAYMYNSD---KDTVERFVLNLATAQVEYSEDQqAMLKTPNTFAVCT----E 1420
Cdd:pfam00169    1 VVKEGWLLKKGGGkKKSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVAS-DSPKRKFCFELRTgertG 79

                           90       100
                   ....*....|....*....|..
gi 2462574518 1421 HRGILLQAASDKDMHDWLYAFN 1442
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAIQ 101

Kinesin motor, catalytic domain. ATPase; Microtubule-dependent molecular motors that play important roles in intracellular transport of organelles and in cell division.

                            10        20        30
                    ....*....|....*....|....*....|....*
gi 2462574518     1 MVAALSPADINYDETLSTLRYADRAKQIRCNAVIN 35
Cdd:smart00129  301 MIANVSPSSSNLEETLSTLRFASRAKEIKNKPIVN 335

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518 1349 VSKKGYLHFLEPHTSGWARRFVVVRRPYAYMYNSDKDTVERFVLNL----ATAQVEysedqqaMLKTPNTFAVCTEHRGI 1424
Cdd:cd13298      6 VLKSGYLLKRSRKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLsellAVAPLK-------DKKRKNVFGIYTPSKNL 78

                           90
                   ....*....|....*...
gi 2462574518 1425 LLQAASDKDMHDWLYAFN 1442
Cdd:cd13298     79 HFRATSEKDANEWVEALR 96

kinesin-12 family protein; Provisional

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462574518    1 MVAALSPADINYDETLSTLRYADRAKQIRCNAVINE---DPNNKL---IRELKDEVTRLRD 55
Cdd:PLN03188   407 MVCAISPSQSCKSETFSTLRFAQRAKAIKNKAVVNEvmqDDVNFLrevIRQLRDELQRVKA 467

FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462574518  190 TRVGREDgerRQDIVLSGHFIKEEHCVFRSDSRGgseaVVTLEPC-EGADTYVNGKKVT-EPSILRSGNRI 258
Cdd:pfam00498    1 VTIGRSP---DCDIVLDDPSVSRRHAEIRYDGGG----RFYLEDLgSTNGTFVNGQRLGpEPVRLKDGDVI 64

forkhead associated (FHA) domain found in the Ras-associating and dilute domain-containing protein (Radil)-like family; The Radil-like family includes Radil and Ras-interacting protein 1 (Rain). Radil acts as an important small GTPase Rap1 effector required for cell spreading and migration. It regulates neutrophil adhesion and motility by linking Rap1 to beta2-integrin activation. Rain, also called Rasip1, is an endothelial-specific Ras-interacting protein required for the proper formation of vascular structures that develop via both vasculogenesis and angiogenesis. It acts as a critical and vascular-specific regulator of GTPase signaling, cell architecture, and adhesion, which is essential for endothelial cell morphogenesis and blood vessel tubulogenesis. Rain interacts with Ras in a GTP-dependent manner and may serve as an effector for endomembrane-associated Ras. Both Radil and Rain contain an FHA domain. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  165 TPHLVNLNEDPLMSECLLYYIKDGITRVGRED-GERRQDIVLSGHFIKEEHCVFR----------SDSRGGSEAVVTLEP 233
Cdd:cd22712      3 YPYLLTLRGFSPKQDLLVYPLLEQVILVGSRTeGARKVDISLRAPDILPQHCWIRrkpeplsddeDSDKESADYRVVLSP 82

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462574518  234 CEGADTYVNGKKVTEPSILRSGNRIIMGKSHVFRFNHP 271
Cdd:cd22712     83 LRGAHVTVNGVPVLSETELHPGDLLGIGEHYLFLFKDP 120

Kinesin motor domain; Kinesin motor domain. This catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases. Kinesins are microtubule-dependent molecular motors that play important roles in intracellular transport and in cell division. In most kinesins, the motor domain is found at the N-terminus (N-type), in some its is found in the middle (M-type), or C-terminal (C-type). N-type and M-type kinesins are (+) end-directed motors, while C-type kinesins are (-) end-directed motors, i.e. they transport cargo towards the (-) end of the microtubule. Kinesin motor domains hydrolyze ATP at a rate of about 80 per second, and move along the microtubule at a speed of about 6400 Angstroms per second. To achieve that, kinesin head groups work in pairs. Upon replacing ADP with ATP, a kinesin motor domain increases its affinity for microtubule binding and locks in place. Also, the neck linker binds to the motor domain, which repositions the other head domain through the coiled-coil domain close to a second tubulin dimer, about 80 Angstroms along the microtubule. Meanwhile, ATP hydrolysis takes place, and when the second head domain binds to the microtubule, the first domain again replaces ADP with ATP, triggering a conformational change that pulls the first domain forward.

                           10        20
                   ....*....|....*....|....*.
gi 2462574518    1 MVAALSPADINYDETLSTLRYADRAK 26
Cdd:cd00106    301 MIACISPSSENFEETLSTLRFASRAK 326

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518 1351 KKGYLHFLEPHTS-GWARRFVVVRRPYAYMYNSDKD--TVERFVLNLaTAQVEYSEDQQamLKTPNTFAVCT-EHRGILL 1426
Cdd:cd00821      1 KEGYLLKRGGGGLkSWKKRWFVLFEGVLLYYKSKKDssYKPKGSIPL-SGILEVEEVSP--KERPHCFELVTpDGRTYYL 77

                           90
                   ....*....|....*
gi 2462574518 1427 QAASDKDMHDWLYAF 1441
Cdd:cd00821     78 QADSEEERQEWLKAL 92

Kinesin motor domain, KIP3-like subgroup; Kinesin motor domain, KIP3-like subgroup. The yeast kinesin KIP3 plays a role in positioning the mitotic spindle. This catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases. Kinesins are microtubule-dependent molecular motors that play important roles in intracellular transport and in cell division. In most kinesins, the motor domain is found at the N-terminus (N-type). N-type kinesins are (+) end-directed motors, i.e. they transport cargo towards the (+) end of the microtubule. Kinesin motor domains hydrolyze ATP at a rate of about 80 per second, and move along the microtubule at a speed of about 6400 Angstroms per second. To achieve that, kinesin head groups work in pairs. Upon replacing ADP with ATP, a kinesin motor domain increases its affinity for microtubule binding and locks in place. Also, the neck linker binds to the motor domain, which repositions the other head domain through the coiled-coil domain close to a second tubulin dimer, about 80 Angstroms along the microtubule. Meanwhile, ATP hydrolysis takes place, and when the second head domain binds to the microtubule, the first domain again replaces ADP with ATP, triggering a conformational change that pulls the first domain forward.

                           10        20
                   ....*....|....*....|....*...
gi 2462574518    1 MVAALSPADINYDETLSTLRYADRAKQI 28
Cdd:cd01370    318 MIANISPSSSSYEETHNTLKYANRAKNI 345

Kinesin motor domain, KIF15-like subgroup; Kinesin motor domain, KIF15-like subgroup. Members of this subgroup seem to play a role in mitosis and meiosis. This catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases. Kinesins are microtubule-dependent molecular motors that play important roles in intracellular transport and in cell division. In most kinesins, the motor domain is found at the N-terminus (N-type). N-type kinesins are (+) end-directed motors, i.e. they transport cargo towards the (+) end of the microtubule. Kinesin motor domains hydrolyze ATP at a rate of about 80 per second, and move along the microtubule at a speed of about 6400 Angstroms per second. To achieve that, kinesin head groups work in pairs. Upon replacing ADP with ATP, a kinesin motor domain increases its affinity for microtubule binding and locks in place. Also, the neck linker binds to the motor domain, which repositions the other head domain through the coiled-coil domain close to a second tubulin dimer, about 80 Angstroms along the microtubule. Meanwhile, ATP hydrolysis takes place, and when the second head domain binds to the microtubule, the first domain again replaces ADP with ATP, triggering a conformational change that pulls the first domain forward.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2462574518    1 MVAALSPADINYDETLSTLRYADRAKQIRCNAVINED 37
Cdd:cd01373    310 IIANVHPSSKCFGETLSTLRFAQRAKLIKNKAVVNED 346

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518 1351 KKGYLhFLEPHTSG--WARRFVVVR--RPYaYMYNSDKDTVERFVLNLATAQVEYSEDqqamLKTPNTFAVCTEHRGILL 1426
Cdd:cd13250      1 KEGYL-FKRSSNAFktWKRRWFSLQngQLY-YQKRDKKDEPTVMVEDLRLCTVKPTED----SDRRFCFEVISPTKSYML 74

                           90
                   ....*....|....
gi 2462574518 1427 QAASDKDMHDWLYA 1440
Cdd:cd13250     75 QAESEEDRQAWIQA 88

forkhead associated (FHA) domain found in proliferation marker protein Ki-67 and similar proteins; Ki-67, also called antigen identified by monoclonal antibody Ki-67, antigen KI-67, or antigen Ki67, acts as a biological surfactant to disperse mitotic chromosomes. It is required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly. Ki-67 binds DNA with a preference for supercoiled DNA and AT-rich DNA. It may also play a role in chromatin organization. Ki-67 contains an FHA domain at its N-terminus. The FHA domain is a small phosphopeptide recognition module.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462574518  185 IKDGITRVGREDgerRQDIVLSGHFIKEEHCVFRSDSRGgseaVVTLEP-CEGADTYVNGKKVTEPSILRSGNRIIMGKs 263
Cdd:cd22673     18 LTKKSCTFGRDL---SCDIRIQLPGVSREHCRIEVDENG----KAYLENlSTTNPTLVNGKAIEKSAELKDGDVITIGG- 89

                   ....*
gi 2462574518  264 HVFRF 268
Cdd:cd22673     90 RSFRF 94