P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

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gi 33598958  21 LANKQDKEGALGEADVIECLSLEKLVNEHKCLCQIEPCSAISGYGKKIDKSIKKGLYWLLHV 82
Cdd:cd04161 106 LANKQDKKNALLGADVIEYLSLEKLVNENKSLCHIEPCSAIEGLGKKIDPSIVEGLRWLLAA 167

Arl2-like protein 1 (Arl2l1) and Arl13; Arl2l1 (Arl2-like protein 1) and Arl13 form a subfamily of the Arf family of small GTPases. Arl2l1 was identified in human cells during a search for the gene(s) responsible for Bardet-Biedl syndrome (BBS). Like Arl6, the identified BBS gene, Arl2l1 is proposed to have cilia-specific functions. Arl13 is found on the X chromosome, but its expression has not been confirmed; it may be a pseudogene.

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                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33598958  21 LANKQDKEGALGEADVIECLSLEKLVNEHKCLCQIEPCSAISGYGKKIDKSIKKGLYWLLHV 82
Cdd:cd04161 106 LANKQDKKNALLGADVIEYLSLEKLVNENKSLCHIEPCSAIEGLGKKIDPSIVEGLRWLLAA 167

PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins. CCDC47 is required to maintain the stability of Asterix. CCDC47 is associated with various membrane-associated processes and is component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis. It is also involved in the regulation of calcium ion homeostasis in the ER, being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway.

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                  ....*....|....*....|....*....|....*....|...
gi 33598958    92 ERIQKETTEQRALEEQEKQERAERVRKLREERKQNEQEQAELD 134
Cdd:pfam07946 271 EKIKKAAEEERAEEAQEKKEEAKKKEREEKLAKLSPEEQRKYE 313

Arl2-like protein 1 (Arl2l1) and Arl13; Arl2l1 (Arl2-like protein 1) and Arl13 form a subfamily of the Arf family of small GTPases. Arl2l1 was identified in human cells during a search for the gene(s) responsible for Bardet-Biedl syndrome (BBS). Like Arl6, the identified BBS gene, Arl2l1 is proposed to have cilia-specific functions. Arl13 is found on the X chromosome, but its expression has not been confirmed; it may be a pseudogene.

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                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33598958  21 LANKQDKEGALGEADVIECLSLEKLVNEHKCLCQIEPCSAISGYGKKIDKSIKKGLYWLLHV 82
Cdd:cd04161 106 LANKQDKKNALLGADVIEYLSLEKLVNENKSLCHIEPCSAIEGLGKKIDPSIVEGLRWLLAA 167

Arf-related protein 1 (Arfrp1); Arfrp1 (Arf-related protein 1), formerly known as ARP, is a membrane-associated Arf family member that lacks the N-terminal myristoylation motif. Arfrp1 is mainly associated with the trans-Golgi compartment and the trans-Golgi network, where it regulates the targeting of Arl1 and the GRIP domain-containing proteins, golgin-97 and golgin-245, onto Golgi membranes. It is also involved in the anterograde transport of the vesicular stomatitis virus G protein from the Golgi to the plasma membrane, and in the retrograde transport of TGN38 and Shiga toxin from endosomes to the trans-Golgi network. Arfrp1 also inhibits Arf/Sec7-dependent activation of phospholipase D. Deletion of Arfrp1 in mice causes embryonic lethality at the gastrulation stage and apoptosis of mesodermal cells, indicating its importance in development.

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gi 33598958  21 LANKQDKEGALGEADVIECLSLeKLVNEHKCLCQIEPCSAISGYGkkidksIKKGLYWL 79
Cdd:cd04160 114 LANKQDLPDALSVAEIKEVFDD-CIALIGRRDCLVQPVSALEGEG------VEEGIEWL 165

Arf-like 5 (Arl5) and 8 (Arl8) GTPases; Arl5/Arl8 subfamily. Arl5 (Arf-like 5) and Arl8, like Arl4 and Arl7, are localized to the nucleus and nucleolus. Arl5 is developmentally regulated during embryogenesis in mice. Human Arl5 interacts with the heterochromatin protein 1-alpha (HP1alpha), a nonhistone chromosomal protein that is associated with heterochromatin and telomeres, and prevents telomere fusion. Arl5 may also play a role in embryonic nuclear dynamics and/or signaling cascades. Arl8 was identified from a fetal cartilage cDNA library. It is found in brain, heart, lung, cartilage, and kidney. No function has been assigned for Arl8 to date.

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                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33598958  21 LANKQDKEGALGEADVIECLSLEKlVNEHKclCQIEPCSAISGygkkidKSIKKGLYWLLH 81
Cdd:cd04153 122 LANKQDLKGAMTPAEISESLGLTS-IRDHT--WHIQGCCALTG------EGLPEGLDWIAS 173

Arf-like 2 (Arl2) GTPase; Arl2 (Arf-like 2) GTPases are members of the Arf family that bind GDP and GTP with very low affinity. Unlike most Arf family proteins, Arl2 is not myristoylated at its N-terminal helix. The protein PDE-delta, first identified in photoreceptor rod cells, binds specifically to Arl2 and is structurally very similar to RhoGDI. Despite the high structural similarity between Arl2 and Rho proteins and between PDE-delta and RhoGDI, the interactions between the GTPases and their effectors are very different. In its GTP bound form, Arl2 interacts with the protein Binder of Arl2 (BART), and the complex is believed to play a role in mitochondrial adenine nucleotide transport. In its GDP bound form, Arl2 interacts with tubulin- folding Cofactor D; this interaction is believed to play a role in regulation of microtubule dynamics that impact the cytoskeleton, cell division, and cytokinesis.

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gi 33598958  21 LANKQDKEGALGEADVIECLSLEKLVNEHKCLCqiePCSAISGYGkkidksIKKGLYWLL 80
Cdd:cd04154 121 FANKQDLPGALSPEEIREVLELDSIKSHHWRIF---GCSAVTGEN------LLDGIDWLV 171

PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins. CCDC47 is required to maintain the stability of Asterix. CCDC47 is associated with various membrane-associated processes and is component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis. It is also involved in the regulation of calcium ion homeostasis in the ER, being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway.

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                  ....*....|....*....|....*....|....*....|...
gi 33598958    92 ERIQKETTEQRALEEQEKQERAERVRKLREERKQNEQEQAELD 134
Cdd:pfam07946 271 EKIKKAAEEERAEEAQEKKEEAKKKEREEKLAKLSPEEQRKYE 313

Arf-like 3 (Arl3) GTPase; Arl3 (Arf-like 3) is an Arf family protein that differs from most Arf family members in the N-terminal extension. In is inactive, GDP-bound form, the N-terminal extension forms an elongated loop that is hydrophobically anchored into the membrane surface; however, it has been proposed that this region might form a helix in the GTP-bound form. The delta subunit of the rod-specific cyclic GMP phosphodiesterase type 6 (PDEdelta) is an Arl3 effector. Arl3 binds microtubules in a regulated manner to alter specific aspects of cytokinesis via interactions with retinitis pigmentosa 2 (RP2). It has been proposed that RP2 functions in concert with Arl3 to link the cell membrane and the cytoskeleton in photoreceptors as part of the cell signaling or vesicular transport machinery. In mice, the absence of Arl3 is associated with abnormal epithelial cell proliferation and cyst formation.

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gi 33598958  21 LANKQDKEGALGEADVIECLSLEKLVNEhkcLCQIEPCSAISGYGkkidksIKKGLYWL 79
Cdd:cd04155 122 FANKQDLLTAAPAEEVAEALNLHDIRDR---SWHIQACSAKTGEG------LQEGMNWV 171