FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; RUFY4 belongs to the FUFY protein family which is characterized by the presence of an N-terminal RUN domain and a C-terminal FYVE domain. The FYVE domain of RUFY4 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue). The biological function of RUFY4 still remains unclear.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 169808409 428 HCIGCNKVFRRLSRRYPCRLCGGLVCHACSVDYK--------KRERCCPTC 470
Cdd:cd15745    1 ACAICAKAFSLFRRKYVCRLCGGVVCHSCSSEDLvlsvpdtcIYLRVCKTC 51

Coiled-coil domain-containing protein 22; Human coiled-coil domain-containing protein 22 (CCDC22) is involved in regulation of NF-kappa-B signalling; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. It is part of the OMMD/CCDC22/CCDC93 (CCC) complex, which interacts with the multisubunit WASH complex required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer. This entry also includes CCDC22 homologs from animals and plants.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409  120 SRGEQLQEPdTGGTSCLQDATREDRTPDLCKPLQPSHLPTflEEKREDSRSLsCPQSTWETEREGFQLDQKDGGPKPRKF 199
Cdd:pfam05667 111 ESSEAADQP-VGKSAVLQRAIAAAIRSQLAAPWLPPECKP--HQRRQGSRAL-RPFHTQTLVLPGRKGKTLKNSKELKEF 186

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409  200 LENSTASIQQQRSRAKDVKMQLTGRKVEGKGSLSGTEDQRTTEGIQKRAADWDLGQGLMAPGLQGREDA--ELGYRCEWN 277
Cdd:pfam05667 187 YSEYLPPVTAQPSSRASVVPSLLERNAAELAAAQEWEEEWNSQGLASRLTPEEYRKRKRTKLLKRIAEQlrSAALAGTEA 266

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409  278 QPDVLRQSWVLGTKKSSPTEKPQEWTGVTSGTMQEDGSEVPLQQEvikDPGYGLQLAKEQAQCQEQLRAQEAELQALQEQ 357
Cdd:pfam05667 267 TSGASRSAQDLAELLSSFSGSSTTDTGLTKGSRFTHTEKLQFTNE---APAATSSPPTKVETEEELQQQREEELEELQEQ 343

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 169808409  358 LSRCQ-------KERALLQVKLEQKQQEAERRDAMyQTELEGQRDLvqamKRRVLELIHEKDLQWQRLQQL 421
Cdd:pfam05667 344 LEDLEssiqeleKEIKKLESSIKQVEEELEELKEQ-NEELEKQYKV----KKKTLDLLPDAEENIAKLQAL 409

FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; RUFY4 belongs to the FUFY protein family which is characterized by the presence of an N-terminal RUN domain and a C-terminal FYVE domain. The FYVE domain of RUFY4 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue). The biological function of RUFY4 still remains unclear.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 169808409 428 HCIGCNKVFRRLSRRYPCRLCGGLVCHACSVDYK--------KRERCCPTC 470
Cdd:cd15745    1 ACAICAKAFSLFRRKYVCRLCGGVVCHSCSSEDLvlsvpdtcIYLRVCKTC 51

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 169808409   428 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS--------VDYKKRERCCPTCAQ 472
Cdd:smart00064  12 NCMGCGKEFNLTKRRHHCRNCGRIFCSKCSskkaplpkLGIERPVRVCDDCYE 64

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409  332 QLAKEQAQCQEQLRAQEAELQALQEQLsrcQKERALLQVKLEQKQQEAERRDAMYQTELEGQRDLVQAMKRRVLELIHEK 411
Cdd:pfam03938  23 QLEKKFKKRQAELEAKQKELQKLYEEL---QKDGALLEEEREEKEQELQKKEQELQQLQQKAQQELQKKQQELLQPIQDK 99

RUN domain; This domain is present in several proteins that are linked to the functions of GTPases in the Rap and Rab families. They could hence play important roles in multiple Ras-like GTPase signalling pathways. The domain is comprises six conserved regions, which in some proteins have considerable insertions between them. The domain core is thought to take up a predominantly alpha fold, with basic amino acids in regions A and D possibly playing a functional role in interactions with Ras GTPases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 169808409   11 KTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNLDL 79
Cdd:pfam02759  64 YSPDGRGRAWIRLALNEKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGEILLGLLVGLSALDFNLCL 132

Coiled-coil domain of Signal Transducer and Activator of Transcription 5 (STAT5); This family consists of the coiled-coil (alpha) domain of the STAT5 proteins (Signal Transducer and Activator of Transcription 5, or Signal Transduction And Transcription 5) which include STAT5A and STAT5B, both of which are >90% identical despite being encoded by separate genes. The coiled-coil domain (CCD) of STAT5A and STAT5B appears to be required for constitutive nuclear localization signals (NLS) function; small deletions within the CCD can abrogate nuclear import. Studies show that the CCD binds to the importin-alpha3 NLS adapter in most cells. STAT5A and STAT5B regulate erythropoiesis, lymphopoiesis, and the maintenance of the hematopoietic stem cell population. STAT5A and STAT5B have overlapping and redundant functions; both isoforms can be activated by the same set of cytokines, but some cytokines preferentially activate either STAT5A or STAT5B, e.g. during pregnancy and lactation, STAT5A rather than STAT5B is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. STAT5 has been found to be constitutively phosphorylated in cancer cells, and therefore constantly activated, either by aberrant cell signaling expression or by mutations. It differentially regulates cellular behavior in human mammary carcinoma. Prolactin (PRL) in the prostate gland can induce growth and survival of prostate cancer cells and tissues through the activation of STAT5, its downstream target; PRL expression and STAT5 activation correlates with disease severity. STAT5A and STAT5B are central signaling molecules in leukemias driven by Abelson fusion tyrosine kinases, displaying unique nuclear shuttling mechanisms and having a key role in resistance of leukemic cells against treatment with tyrosine kinase inhibitors (TKI). In addition, STAT5A and STAT5B promote survival of leukemic stem cells. STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis via the induction of the expression of Id genes. Autosomal recessive STAT5B mutations are associated with severe growth failure, insulin-like growth factor (IGF) deficiency and growth hormone insensitivity (GHI) syndrome. STAT5B deficiency can lead to potentially fatal primary immunodeficiency.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 339 QCQEQLRAQeAELQALQEQ-LSRCQKERALLQVKLEQKQQEAerrDAMYQTELEGQRDLVQAMK------RRVLELIHEK 411
Cdd:cd16855   37 QYQESQKIQ-AQLQQLQQQpQNERIELEQQLQQQKEQLEQLL---NAKAQELLQLRMELADKFKktiqllSKLQSRVLDE 112

                         90
                 ....*....|..
gi 169808409 412 DL-QWQRLQQLS 422
Cdd:cd16855  113 ELiQWKRQQQLA 124

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409   332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRDAMYQ---TELEGQRDLVQAMKRRVLELI 408
Cdd:TIGR02168  313 NLERQLEELEAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEeleSRLEELEEQLETLRSKVAQLE 392

                           90
                   ....*....|....*
gi 169808409   409 HEKDLQWQRLQQLST 423
Cdd:TIGR02168  393 LQIASLNNEIERLEA 407

RUN domain found in RUN and FYVE domain-containing protein 4 (RUFY4), FYVE and coiled-coil domain-containing protein 1 (FYCO1), and similar proteins; The family includes RUFY4 and FYCO1. RUFY4 acts as a positive regulator that enhances autophagy and lysosome tethering in response to Interleukin-4. It is expressed in a cell-specific manner or under specific immunological conditions associated with IL4 expression such as allergic asthma. FYCO1, also called zinc finger FYVE domain-containing protein 7 (ZFYVE7), is a multidomain autophagy adaptor protein that interacts with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7, and phosphatidylinositol 3-phosphate (PI3P), to mediate microtubule plus-end-directed autophagosome transport. Both RUFY4 and FYCO1 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between; this model represents the RUN domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 169808409   2 SFICSQDKLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNL 77
Cdd:cd17682   75 KFVKSCKKVKTNQGRGRLFIRYALNKKCLHDPVQQLVKNPKLLSDYYSPDSILGNEILSEILLSLLYQLNEINFDL 150

RUN domain; RUN domain, named after RPIP8 (Rap2 interacting protein 8), UNC-14 and NESCA (new molecule containing SH3 at the carboxyl-terminus), is a less conserved protein motif that comprises six conserved regions, which in some proteins have considerable insertions between them. The domain core is thought to take up a predominantly alpha fold, with basic amino acids in regions A and D possibly playing a functional role in interactions with Ras GTPases. RUN domains are often found in proteins linked particularly to the functions of GTPases in the Rap and Rab families, suggesting the RUN domain may be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. RUN domain-containing proteins could hence play important roles in multiple Ras-like GTPase signalling pathways.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 169808409   4 ICSQDKLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNL 77
Cdd:cd17671   81 INSLSNVKTDDGRGRAWIRLALNEKSLESYLAALLSDQSLLRKYYEPWALLRDPEEAELFLSLLVGLSSLDFNL 154

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 169808409 428 HCIGCNKVFRRLSRRYPCRLCGGLVCHACSV--------DYKKRERCCPTCA 471
Cdd:cd00065    1 RCMLCGKKFSLFRRRHHCRRCGRVFCSKCSSkklplpsfGSGKPVRVCDSCY 52

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 169808409  428 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS---------VDYKKRERCCPTCAQQ 473
Cdd:pfam01363  11 VCMICSKPFTFFRRRHHCRNCGRVFCSACSskkisllpeLGSNKPVRVCDACYDT 65

FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and similar proteins; Rbsn-5, also termed zinc finger FYVE domain-containing protein 20, is a novel Rab5 effector that is complexed to the Sec1-like protein VPS45 and recruited in a phosphatidylinositol-3-kinase-dependent fashion to early endosomes. It also binds to Rab4 and EHD1/RME-1, two regulators of the recycling route, and is involved in cargo recycling to the plasma membrane. Moreover, Rbsn-5 regulates endocytosis at the apical side of the wing epithelium and plays a role of the apical endocytic trafficking of Fmi in the establishment of planar cell polarity (PCP).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 169808409 429 CIGCNKVFRRLSRRYPCRLCGGLVCHACSVDYKKRERCCPTC 470
Cdd:cd15716   13 CPDCGKKFNLARRRHHCRLCGSIMCNKCSQFLPLHIRCCHHC 54

RUN domain found in RUN and FYVE domain-containing proteins, RUFY1, RUFY2, RUFY3 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1, RUFY2, and RUFY3. RUFY1, also called FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homolog of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY2, also called Rab4-interacting protein related, is a novel embryonic factor that is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. RUFY3, also called Rap2-interacting protein x (RIPx or RPIPx), or single axon-regulated protein (singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5. RUFY1, RUFY2, and RUFY3 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between; this model represents the RUN domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 169808409  10 LKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEdILDSLYALNGVAFNL 77
Cdd:cd17681   89 IKTPLGRARAWLRLALMQKKLADYFRALIENKDLLSEFYEPGALMMSEEAVV-IAGLLVGLNVIDCNL 155

RUN domain found in RUN domain-containing protein 3 (RUNDC3) and similar proteins; RUNDC3 contains two isoforms, RUNDC3A and RUNDC3B. RUNDC3A, also called Rap2-interacting protein 8 (RPIP8), may act as an effector of Rap2A GTPase in neuronal cells. RUNDC3B, also called Rap2-binding protein 9, or Rap2-interacting protein 9 (RPIP-9), contains a RUN domain in its N-terminal region that mediates interaction with Rap2, an important component of the Mitogen-Activated Protein Kinase (MAPK) cascade, which regulates cellular proliferation and differentiation. It also contains characteristic binding sites for MAPK intermediates. Both RUNDC3A and RUNDC3B contain a RUN domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 169808409   4 ICSQDKLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLlcaeLQED---ILDSLYALNGVAFNL 77
Cdd:cd17684   78 IEQMENIKSPKAKGRAWIRVALMEKRLSEYLSTALKQTRLTRNFYQDGAIM----LSEDatvLCGMLIGLNAIDFSF 150

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409  332 QLAKEQAQCQEQLRAQEAELQALQEQLsrcQKERALLQVKLEQKQQEAERRDAMYQTELEGQRDLVQAMKRRVLELIHEK 411
Cdd:pfam03938  23 QLEKKFKKRQAELEAKQKELQKLYEEL---QKDGALLEEEREEKEQELQKKEQELQQLQQKAQQELQKKQQELLQPIQDK 99

RUN domain; This domain is present in several proteins that are linked to the functions of GTPases in the Rap and Rab families. They could hence play important roles in multiple Ras-like GTPase signalling pathways. The domain is comprises six conserved regions, which in some proteins have considerable insertions between them. The domain core is thought to take up a predominantly alpha fold, with basic amino acids in regions A and D possibly playing a functional role in interactions with Ras GTPases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 169808409   11 KTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNLDL 79
Cdd:pfam02759  64 YSPDGRGRAWIRLALNEKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGEILLGLLVGLSALDFNLCL 132

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 341 QEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRDAmyqtELEGQRDLVQAMKRRVLELIHEKDLQWQRLQQ 420
Cdd:COG1196  238 EAELEELEAELEELEAELEELEAELAELEAELEELRLELEELEL----ELEEAQAEEYELLAELARLEQDIARLEERRRE 313

                 ..
gi 169808409 421 LS 422
Cdd:COG1196  314 LE 315

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRDAMYQTELEGQRDLVQAMKRRVLELIHEK 411
Cdd:COG1196  313 ELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEAL 392

                         90
                 ....*....|
gi 169808409 412 DLQWQRLQQL 421
Cdd:COG1196  393 RAAAELAAQL 402

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRDAMYQTELEGQRDLVQAMKRRVLELIHEK 411
Cdd:COG1196  320 ELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELA 399

                         90
                 ....*....|.
gi 169808409 412 DLQWQRLQQLS 422
Cdd:COG1196  400 AQLEELEEAEE 410

FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also termed FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2), or zinc finger FYVE domain-containing protein 11, is an dual specificity protein phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). It is localizes to early endosomes, as well as to Rab11- and Sec15-positive recycling endosomes, and regulates sorting from early endosomes. Moreover, MTMR4 is preferentially associated with and dephosphorylated the activated regulatory Smad proteins (R-Smads) in cytoplasm to keep transforming growth factor (TGF) beta signaling in homeostasis. It also functions as an essential negative modulator for the homeostasis of bone morphogenetic protein (BMP)/decapentaplegic (Dpp) signaling. In addition, MTMR4 acts as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4) and may play a role in the biological process of muscle breakdown. MTMR4 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 169808409 425 APGHCIGCNKVFRRLSRRYPCRLCGGLVCHACS 457
Cdd:cd15733    6 AASHCFGCDCEFWLAKRKHHCRNCGNVFCADCS 38

FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 169808409 428 HCIGCNKVFRRLSRRYPCRLCGGLVCHACSVD------YKKRERCCPTC 470
Cdd:cd15758   14 HCKQCEKEFSISRRKHHCRNCGHIFCNTCSSNelalpsYPKPVRVCDSC 62

Type IV pilus assembly protein PilN [Cell motility, Extracellular structures];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 341 QEQLRAQEAELQALQEQLSrcqkerallqvKLEQKQQEAErrdamyqtELEGQRDLVQAmKRRVLELIHEKDLQWQR-LQ 419
Cdd:COG3166   44 QGQIAQQQARNAALQQEIA-----------KLDKQIAEIK--------ELKKQKAELLA-RLQVIEQLQQSRPPWVHlLD 103

                 ....*..
gi 169808409 420 QLSTVAP 426
Cdd:COG3166  104 ELARLLP 110

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), and similar proteins; This family includes protein containing both PH and FYVE domains 1 (phafin-1) and 2 (phafin-2). Phafin-1 is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway. Phafin-2 is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 169808409 429 CIGCNKV-FRRLSRRYPCRLCGGLVCHACS-------VDYKKRERCCPTC 470
Cdd:cd15717   11 CMHCKKTkFTAINRRHHCRKCGAVVCGACSskkfllpHQSSKPLRVCDTC 60

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQ---QEAERRDAMYQTELEGQRDLVQAMKRRVLELI 408
Cdd:COG4372   42 KLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNeqlQAAQAELAQAQEELESLQEEAEELQEELEELQ 121

                         90
                 ....*....|...
gi 169808409 409 HEKDLQWQRLQQL 421
Cdd:COG4372  122 KERQDLEQQRKQL 134

RUN domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; RUFY1, also called FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homolog of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between; this model represents the RUN domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 169808409   9 KLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSpLLCAELQEDILDSLYALNGVAFNL 77
Cdd:cd17694   88 ELKTAVGRGRAWLHLALMQKKLADYLKVLIDRKDLLSEFYEPGA-LMMEEEGAVIVGLLVGLNVIDANL 155

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRDAMYQTELEGQRDLVQAMKRR 403
Cdd:COG4942  164 ALRAELEAERAELEALLAELEEERAALEALKAERQKLLARLEKELAELAAELAELQQEAEELEALIARLEAE 235

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRdamyQTELEGQRDLVQAM 400
Cdd:COG3883   27 ELQAELEAAQAELDALQAELEELNEEYNELQAELEALQAEIDKLQAEIAEA----EAEIEERREELGER 91

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRDAMYQTELEGQRDLVQAMKRRVLELIHEK 411
Cdd:COG3883  126 KIADADADLLEELKADKAELEAKKAELEAKLAELEALKAELEAAKAELEAQQAEQEALLAQLSAEEAAAEAQLAELEAEL 205

                 ....*....
gi 169808409 412 DLQWQRLQQ 420
Cdd:COG3883  206 AAAEAAAAA 214

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQKQQEAERRDAMYQTELEGQRDLVQAMKRRVLEL 407
Cdd:COG4942  150 EQAEELRADLAELAALRAELEAERAELEALLAELEEERAALEALKAERQKLLARLEKELAELAAELAELQQEAEEL 225

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 169808409 332 QLAKEQAQCQEQLRAQEAELQALQEQLSRCQKERALLQVKLEQ----------KQQEAERRDAMYQTELEGQRDLVQAMK 401
Cdd:COG1196  257 ELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARleqdiarleeRRRELEERLEELEEELAELEEELEELE 336

                         90       100
                 ....*....|....*....|
gi 169808409 402 RRVLELIHEKDLQWQRLQQL 421
Cdd:COG1196  337 EELEELEEELEEAEEELEEA 356

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and similar proteins; scVps27p, also termed Golgi retention defective protein 11, is the putative yeast counterpart of the mammalian protein Hrs and is involved in endosome maturation. It is a mono-ubiquitin-binding protein that interacts with ubiquitinated cargoes, such as Hse1p, and is required for protein sorting into the multivesicular body. Vps27p forms a complex with Hse1p. The complex binds ubiquitin and mediates endosomal protein sorting. At the endosome, Vps27p and a trimeric protein complex, ESCRT-1, bind ubiquitin and are important for multivesicular body (MVB) sorting. Vps27p contains an N-terminal VHS (Vps27/Hrs/STAM) domain, a FYVE domain that binds PtdIns3P, followed by two ubiquitin-interacting motifs (UIMs), and a C-terminal clathrin-binding motif.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 169808409 428 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS---------VDYKKRERCCPTCA 471
Cdd:cd15760    7 RCDVCRKKFGLFKRRHHCRNCGDSFCSEHSsrriplphlGPLGVPQRVCDRCF 59

FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, also termed FYVE finger-containing phosphoinositide kinase, or 1-phosphatidylinositol 3-phosphate 5-kinase, or phosphatidylinositol 3-phosphate 5-kinase (PIP5K3), or phosphatidylinositol 3-phosphate 5-kinase type III (PIPkin-III or type III PIP kinase), is a phosphoinositide 5-kinase that forms a complex with its regulators, the scaffolding protein Vac14 and the lipid phosphatase Fig4. The complex is responsible for synthesizing phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] from phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). Then phosphatidylinositol-5-phosphate (PtdIns5P) is generated directly from PtdIns(3,5)P2. PtdIns(3,5)P2 and PtdIns5P regulate endosomal trafficking and responses to extracellular stimuli. At this point, PIKfyve is vital in early embryonic development. Moreover, PIKfyve forms a complex with ArPIKfyve (associated regulator of PIKfyve) and SAC3 at the endomembranes, which plays a role in receptor tyrosine kinase (RTK) degradation. The phosphorylation of PIKfyve by AKT can facilitate Epidermal growth factor receptor (EGFR) degradation. In addition, PIKfyve may participate in the regulation of the glutamate transporters EAAT2, EAAT3 and EAAT4, and the cystic fibrosis transmembrane conductance regulator (CFTR). It is also essential for systemic glucose homeostasis and insulin-regulated glucose uptake/GLUT4 translocation in skeletal muscle. It can be activated by protein kinase B (PKB/Akt) and further up-regulates human ether-a-go-go (hERG) channels. This family also includes the yeast and plant orthologs of human PIKfyve, Fab1. PIKfyve and its orthologs share a similar architecture. They contain an N-terminal FYVE domain, a middle region related to the CCT/TCP-1/Cpn60 chaperonins that are involved in productive folding of actin and tubulin, a second middle domain that contains a number of conserved cysteine residues (CCR) unique to this family, and a C-terminal lipid kinase domain related to PtdInsP kinases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 169808409 429 CIGCNKVFRRLSRRYPCRLCGGLVCHACS--------VDYKKRERCCPTCAQ 472
Cdd:cd15725   11 CYECSEKFTTFRRRHHCRLCGQIFCSRCCnqeipgkfIGYPGDLRVCTYCCK 62