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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   4 ERANLMHMMKLSIKVLLQSALSLGRSLDADHAPLQQFFVVMEHCLKHGLKVKKSFIGQNKSFFGPLELVEKLCPEASDIA 83
Cdd:cd17694   1 ERANLMNMMKLSIKVLIQSALSLGRTLDSDYPPLQQFFVVLEHCLKHGLKVKKSFIGQNKSFFGPLELVEKLCPEASDIA 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94721332  84 TSVRNLPELKTAVGRGRAWLYLALMQKKLADYLKVLIDNKHLLSEFYEPEALMMEEEGMVIVGLLVGLNVLDANLC 159
Cdd:cd17694  81 TSARNLPELKTAVGRGRAWLHLALMQKKLADYLKVLIDRKDLLSEFYEPGALMMEEEGAVIVGLLVGLNVIDANLC 156

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 94721332    265 KSVEITKQDTKVELETYKQTRQGLDEMYSDVWKQLKEEKKVRLELEKELELQIGMKTEMEIAMKLLEKDTHEKQDTLVAL 344
Cdd:TIGR02168  701 AELRKELEELEEELEQLRKELEELSRQISALRKDLARLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEA 780

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    345 RQQLEEVKAinlqmfhKAQNAESSLQQKNEAITSFEGKTNQVMSSMKQMEERLQHSERARQGAEERSHKLQQELG---GR 421
Cdd:TIGR02168  781 EAEIEELEA-------QIEQLKEELKALREALDELRAELTLLNEEAANLRERLESLERRIAATERRLEDLEEQIEelsED 853

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    422 IGALQLQLSQLHEQCSSLEKELKSEKEQRQALQRELQhekdtssLLRMELQQVEglkKELRELQDEKAELQKICEEQEQA 501
Cdd:TIGR02168  854 IESLAAEIEELEELIEELESELEALLNERASLEEALA-------LLRSELEELS---EELRELESKRSELRRELEELREK 923

                          250       260
                   ....*....|....*....|
gi 94721332    502 LQEMGLHLSQSKLKMEDIKE 521
Cdd:TIGR02168  924 LAQLELRLEGLEVRIDNLQE 943

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   4 ERANLMHMMKLSIKVLLQSALSLGRSLDADHAPLQQFFVVMEHCLKHGLKVKKSFIGQNKSFFGPLELVEKLCPEASDIA 83
Cdd:cd17694   1 ERANLMNMMKLSIKVLIQSALSLGRTLDSDYPPLQQFFVVLEHCLKHGLKVKKSFIGQNKSFFGPLELVEKLCPEASDIA 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94721332  84 TSVRNLPELKTAVGRGRAWLYLALMQKKLADYLKVLIDNKHLLSEFYEPEALMMEEEGMVIVGLLVGLNVLDANLC 159
Cdd:cd17694  81 TSARNLPELKTAVGRGRAWLHLALMQKKLADYLKVLIDRKDLLSEFYEPGALMMEEEGAVIVGLLVGLNVIDANLC 156

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    39 QFFVVMEHCLKHGLKV------KKSFIGQNKSFFGPLELVEKLCPEASDIATSVRNLPELKTA---VGRGRAWLYLALMQ 109
Cdd:pfam02759   1 QLCAALEALLSHGLKRssllilRAAGLLPERSFWALLERVGKLVPPAEELLSSVQELEQIHTPyspDGRGRAWIRLALNE 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 94721332   110 KKLADYLKVLIDNKHLLSEFYEPEALMMEEEGM-VIVGLLVGLNVLDANLCLKG 162
Cdd:pfam02759  81 KLLDQWLKLLLSNKELLSEYYEPWALLADPEFGeILLGLLVGLSALDFNLCLKL 134

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94721332    531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPS--YPKPVRVCDSCHTLL 591
Cdd:smart00064   4 WIPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKlgIERPVRVCDDCYENL 66

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 94721332    265 KSVEITKQDTKVELETYKQTRQGLDEMYSDVWKQLKEEKKVRLELEKELELQIGMKTEMEIAMKLLEKDTHEKQDTLVAL 344
Cdd:TIGR02168  701 AELRKELEELEEELEQLRKELEELSRQISALRKDLARLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEA 780

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    345 RQQLEEVKAinlqmfhKAQNAESSLQQKNEAITSFEGKTNQVMSSMKQMEERLQHSERARQGAEERSHKLQQELG---GR 421
Cdd:TIGR02168  781 EAEIEELEA-------QIEQLKEELKALREALDELRAELTLLNEEAANLRERLESLERRIAATERRLEDLEEQIEelsED 853

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    422 IGALQLQLSQLHEQCSSLEKELKSEKEQRQALQRELQhekdtssLLRMELQQVEglkKELRELQDEKAELQKICEEQEQA 501
Cdd:TIGR02168  854 IESLAAEIEELEELIEELESELEALLNERASLEEALA-------LLRSELEELS---EELRELESKRSELRRELEELREK 923

                          250       260
                   ....*....|....*....|
gi 94721332    502 LQEMGLHLSQSKLKMEDIKE 521
Cdd:TIGR02168  924 LAQLELRLEGLEVRIDNLQE 943

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    214 VGDLQTKIDGLEKTNSKLQEELSAATDRIcslQEEQQQLREQNELIRErseksVEITKQDTKVELETYKQTRQGLDEMYS 293
Cdd:pfam01576  224 IAELQAQIAELRAQLAKKEEELQAALARL---EEETAQKNNALKKIRE-----LEAQISELQEDLESERAARNKAEKQRR 295

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    294 DVWKQLKEEKKVRLELEKELELQIGMKT--EMEIAM--KLLEKDT--HEKQ---------DTLVALRQQLEEVK--AINL 356
Cdd:pfam01576  296 DLGEELEALKTELEDTLDTTAAQQELRSkrEQEVTElkKALEEETrsHEAQlqemrqkhtQALEELTEQLEQAKrnKANL 375

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    357 QMFHKAQNAESS-----LQQKNEAITSFEGKTNQVMSSMKQMEERLQHSERARQGAEERSHKLQQELGGRIGALqlqlSQ 431
Cdd:pfam01576  376 EKAKQALESENAelqaeLRTLQQAKQDSEHKRKKLEGQLQELQARLSESERQRAELAEKLSKLQSELESVSSLL----NE 451

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332    432 LHEQCSSLEKELKSEKEQRQalqrelqhekDTSSLLRMELQQVEGLKKELRELQDEKAELQKICEEQEQALQEMGLHLSQ 511
Cdd:pfam01576  452 AEGKNIKLSKDVSSLESQLQ----------DTQELLQEETRQKLNLSTRLRQLEDERNSLQEQLEEEEEAKRNVERQLST 521

                   ....*....
gi 94721332    512 SKLKMEDIK 520
Cdd:pfam01576  522 LQAQLSDMK 530

mechanosensitive channel MscK;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   328 KLLEKDTHEKQDTLvalrQQLEEVKAINLQMFHKAQNAESSLQQKNEAITSFEGKTNQVMS------SMKQMEERLqhSE 401
Cdd:PRK11281   59 KLVQQDLEQTLALL----DKIDRQKEETEQLKQQLAQAPAKLRQAQAELEALKDDNDEETRetlstlSLRQLESRL--AQ 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   402 RARQGAEershkLQQELG---GRIGALQLQ-------LSQLHEQCSSLEKELKSEK--------EQRQALQRELQHEKDT 463
Cdd:PRK11281  133 TLDQLQN-----AQNDLAeynSQLVSLQTQperaqaaLYANSQRLQQIRNLLKGGKvggkalrpSQRVLLQAEQALLNAQ 207

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 94721332   464 SSLLRMELQQVEGLKKELRELQDEKAELQKICEEQEQALQE 504
Cdd:PRK11281  208 NDLQRKSLEGNTQLQDLLQKQRDYLTARIQRLEHQLQLLQE 248

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   4 ERANLMHMMKLSIKVLLQSALSLGRSLDADHAPLQQFFVVMEHCLKHGLKVKKSFIGQNKSFFGPLELVEKLCPEASDIA 83
Cdd:cd17694   1 ERANLMNMMKLSIKVLIQSALSLGRTLDSDYPPLQQFFVVLEHCLKHGLKVKKSFIGQNKSFFGPLELVEKLCPEASDIA 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94721332  84 TSVRNLPELKTAVGRGRAWLYLALMQKKLADYLKVLIDNKHLLSEFYEPEALMMEEEGMVIVGLLVGLNVLDANLC 159
Cdd:cd17694  81 TSARNLPELKTAVGRGRAWLHLALMQKKLADYLKVLIDRKDLLSEFYEPGALMMEEEGAVIVGLLVGLNVIDANLC 156

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   4 ERANLMHMMKLSIKVLLQSALSLGRSLDADHAPLQQFFVVMEHCLKHGLKVKKSFIGQNKSFFGPLELVEKLCPEASDIA 83
Cdd:cd17681   1 ERRNLLNLAKLSIKELIESALSFGRTLDSDHVPLQQFFVILEHVLRHGLKVKKSFLGPNKSFWPVLEHVEKLVPEANEIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94721332  84 TSVRNLPELKTAVGRGRAWLYLALMQKKLADYLKVLIDNKHLLSEFYEPEALMMEEEGMVIVGLLVGLNVLDANL 158
Cdd:cd17681  81 ASVRDLPGIKTPLGRARAWLRLALMQKKLADYFRALIENKDLLSEFYEPGALMMSEEAVVIAGLLVGLNVIDCNL 155

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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94721332 526 LKGHAWLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYPKPVRVCDSCHTLLLQRCS 596
Cdd:cd15758   1 LKGHAWLKDDEATHCKQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYPKPVRVCDSCHTLLLQRCS 71

FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1 and RUFY2. 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. RUFY2, also termed 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. Both RUFY1 and RUFY2 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYPKPVRVCDSCH 588
Cdd:cd15721   1 WADDKEVTHCQQCEKEFSLSRRKHHCRNCGGIFCNSCSDNTMPLPSSAKPVRVCDTCY 58

FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed endosome-associated protein p162, or zinc finger FYVE domain-containing protein 2, is an essential component of the endosomal fusion machinery and required for the fusion and maturation of early endosomes in endocytosis. It forms a parallel coiled-coil homodimer in cells. EEA1 serves as the p97 ATPase substrate and the p97 ATPase may regulate the size of early endosomes by governing the oligomeric state of EEA1. It can interact with the GTP-bound form of Rab22a and be involved in endosomal membrane trafficking. EEA1 also functions as an obligate scaffold for angiotensin II-induced Akt activation in early endosomes. It can be phosphorylated by p38 mitogen-activated protein kinase (MAPK) and further regulate mu opioid receptor endocytosis. EEA1 consists of an N-terminal C2H2 Zn2+ finger, four long heptad repeats, and a C-terminal region containing a calmodulin binding (IQ) motif, a Rab5 interaction site, and a FYVE domain. This model corresponds to the FYVE domain that is responsible for binding phosphatidyl inositol-3-phosphate (PtdIns3P or PI3P) on the membrane.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94721332 529 HAWLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYPKPVRVCDSCHTLL 591
Cdd:cd15730   1 RKWADDEEVQNCMACGKGFSVTVRKHHCRQCGNIFCNECSSKTATTPSSKKPVRVCDACFDDL 63

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94721332   531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALP---SYPKPVRVCDSCHTLLLQ 593
Cdd:pfam01363   3 WVPDSSATVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLLpelGSNKPVRVCDACYDTLQK 68

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   7 NLMHMMKLSIKVLLQSALSlgRSLDADHAPLQQFFVVMEHCLKHGLKVKKSFIG--QNKSFFGPLELVEKLCPEASdIAt 84
Cdd:cd17684   1 NLVTVCRLSVKSLIDKACL--ETIDDSSEELINFAAILEQILSHRLKPVKPWYGseEPRTFWDYIRVACKKVPQNC-IA- 76

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94721332  85 SVRNLPELKTAVGRGRAWLYLALMQKKLADYLKVLIDNKHLLSEFYEPEALMMEEEGMVIVGLLVGLNVLDANL 158
Cdd:cd17684  77 SIEQMENIKSPKAKGRAWIRVALMEKRLSEYLSTALKQTRLTRNFYQDGAIMLSEDATVLCGMLIGLNAIDFSF 150

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        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALP--SYPKPVRVCDSCH 588
Cdd:cd15733   1 WVPDHAASHCFGCDCEFWLAKRKHHCRNCGNVFCADCSNYKLPIPdeQLYDPVRVCNSCY 60

FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar proteins; WDFY3, also termed autophagy-linked FYVE protein (Alfy), is a ubiquitously expressed phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein required for selective macroautophagic degradation of aggregated proteins. It regulates the protein degradation through the direct interaction with the autophagy protein Atg5. Moreover, WDFY3 acts as a scaffold that bridges its cargo to the macroautophagic machinery via the creation of a greater complex with Atg12, Atg16L, and LC3. It also functionally associates with sequestosome-1/p62 (SQSTM1) in osteoclasts. WDFY3 shuttles between the nucleus and cytoplasm. It predominantly localizes to the nucleus and nuclear membrane under basal conditions, but is recruited to cytoplasmic ubiquitin-positive protein aggregates under stress conditions. WDFY3 contains a PH-BEACH domain assemblage, five WD40 repeats and a PtdIns3P-binding FYVE domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYP--KPVRVCDSCHTLL 591
Cdd:cd15719   3 WVKDEGGDSCTGCSVRFSLTERRHHCRNCGQLFCSKCSRFESEIRRLRisRPVRVCQACYNIL 65

FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This family includes a group of uncharacterized rab GTPase-binding effector proteins found in bilateria. Although their biological functions remain unclear, they all contain a FYVE domain that harbors a putative phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding site.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNelALPSYP--KPVRVCDSCHTLL 591
Cdd:cd15739   4 WQHEDDVDQCPNCKTPFSVGKRKHHCRHCGKIFCSDCLTK--TVPSGPnrRPARVCDVCHTLL 64

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 94721332 539 HCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPS--YPKPVRVCDSCH 588
Cdd:cd00065   1 RCMLCGKKFSLFRRRHHCRRCGRVFCSKCSSKKLPLPSfgSGKPVRVCDSCY 52

FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also termed Myotubularin-related phosphatase 3, or FYVE domain-containing dual specificity protein phosphatase 1 (FYVE-DSP1), or zinc finger FYVE domain-containing protein 10, is a ubiquitously expressed phosphoinositide 3-phosphatase specific for phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and PIKfyve, which produces PtdIns(3,5)P2 from PtdIns3P. It regulates cell migration through modulating phosphatidylinositol 5-phosphate (PtdIns5P) levels. MTMR3 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain. Unlike conventional FYVE domains, the FYVE domain of MTMR3 neither confers endosomal localization nor binds to PtdIns3P. It is also not required for the enzyme activity of MTMR3. In contrast, the PH-G domain binds phosphoinositides.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYP--KPVRVCDSC 587
Cdd:cd15732   2 WVPDHLAASCYGCEREFWLASRKHHCRNCGNVFCGSCCNQKLPVPSQQlfEPSRVCKSC 60

FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins; Hrs, also termed protein pp110, is a tyrosine phosphorylated protein that plays an important role in the signaling pathway of HGF. It is localized to early endosomes and an essential component of the endosomal sorting and trafficking machinery. Hrs interacts with hypertonia-associated protein Trak1, a novel regulator of endosome-to-lysosome trafficking. It can also forms an Hrs/actinin-4/BERP/myosin V protein complex that is required for efficient transferrin receptor (TfR) recycling but not for epidermal growth factor receptor (EGFR) degradation. Moreover, Hrs, together with STAM proteins, STAM1 and STAM2, and EPs15, forms a multivalent ubiquitin-binding complex that sorts ubiquitinated proteins into the multivesicular body pathway, and plays a regulatory role in endocytosis/exocytosis. Furthermore, Hrs functions as an interactor of the neurofibromatosis 2 tumor suppressor protein schwannomin/merlin. It is also involved in the inhibition of citron kinase-mediated HIV-1 budding. Hrs contains a single ubiquitin-interacting motif (UIM) that is crucial for its function in receptor sorting, and a FYVE domain that harbors double Zn2+ binding sites.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332 531 WLKDDEathCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSY--PKPVRVCDSCH 588
Cdd:cd15720   2 WKDGDE---CHRCRVQFGVFQRKHHCRACGQVFCGKCSSKSSTIPKFgiEKEVRVCDPCY 58

FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar proteins; Phafin-2, also termed endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains (EAPF), or pleckstrin homology domain-containing family F member 2 (PKHF2), or PH domain-containing family F member 2, or PH and FYVE domain-containing protein 2, or zinc finger FYVE domain-containing protein 18, 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94721332 531 WLKDDEATHCRQCEK-EFSISRRKHHCRNCGHIFCNTCSSNELALPSY-PKPVRVCDSCHTLL 591
Cdd:cd15755   2 WVPDSEATVCMRCQKaKFTPVNRRHHCRKCGFVVCGPCSEKKFLLPSQsSKPVRVCDFCYDLL 64

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNEL--ALPSYPKPVRVCDSCH 588
Cdd:cd15725   2 WMPDSSCKECYECSEKFTTFRRRHHCRLCGQIFCSRCCNQEIpgKFIGYPGDLRVCTYCC 61

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSnelalpSYPKPVRVCDSCHTLLLQR 594
Cdd:cd15716   4 WVNDSDVPFCPDCGKKFNLARRRHHCRLCGSIMCNKCSQ------FLPLHIRCCHHCKDLLERR 61

FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar proteins; ANFY1, also termed ankyrin repeats hooked to a zinc finger motif (Ankhzn), is a novel cytoplasmic protein that belongs to a new group of double zinc finger proteins involved in vesicle or protein transport. It is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. ANFY1 contains an N-terminal coiled-coil region and a BTB/POZ domain, ankyrin repeats in the middle, and a C-terminal FYVE domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94721332 536 EATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSY--PKPVRVCDSCHTLL 591
Cdd:cd15728   6 DGDYCYECGVKFGITTRKHHCRHCGRLLCSKCSTKEVPIIKFdlNKPVRVCDVCFDVL 63

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar proteins; FGD6, also termed zinc finger FYVE domain-containing protein 24 is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) whose biological function remains unclear. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Moreover, the FYVE domain of FGD6 is a canonical FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYP-KPVRVCDSC 587
Cdd:cd15743   3 WIPDSRVTMCMICTSEFTVTWRRHHCRACGKVVCGSCSSNKAPLEYLKnKSARVCDEC 60

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94721332 531 WLKDDEATHCRQCEKEF-SISRRKHHCRNCGHIFCNTCSSNELALP-SYPKPVRVCDSCHTLL 591
Cdd:cd15741   3 WVRDNEVTMCMRCKEPFnALTRRRHHCRACGYVVCWKCSDYKATLEyDGNKLNRVCKHCYVIL 65

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332  31 DADHAPLQQFFVVMEHCLKHGLKVKKSFIGQNKSFFGPLE-LVEKLCPEA---SDIATSVRNLPELKTAVGRGRAWLYLA 106
Cdd:cd17682  18 DPDNPYLRPFCETLEKILRKGLKEKVSLGGRRKDYWDWLEeLLKKLNKIPkslSDAVKFVKSCKKVKTNQGRGRLFIRYA 97

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 94721332 107 LMQKKLADYLKVLIDNKHLLSEFYEPEALMMEEE-GMVIVGLLVGLN 152
Cdd:cd17682  98 LNKKCLHDPVQQLVKNPKLLSDYYSPDSILGNEIlSEILLSLLYQLN 144

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar proteins; Phafin-1, also termed lysosome-associated apoptosis-inducing protein containing PH (pleckstrin homology) and FYVE domains (LAPF), or pleckstrin homology domain-containing family F member 1 (PKHF1), or PH domain-containing family F member 1, or apoptosis-inducing protein, or PH and FYVE domain-containing protein 1, or zinc finger FYVE domain-containing protein 15, 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94721332 531 WLKDDEATHCRQC-EKEFSISRRKHHCRNCGHIFCNTCSSNELALPSY-PKPVRVCDSCHTLL 591
Cdd:cd15754   2 WIPDKATDICMRCtQTNFSLLTRRHHCRKCGFVVCHECSRQRFLIPRLsPKPVRVCSLCYRKL 64

FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The family corresponds to the second FYVE domain that is responsible for the ability of Pep7p to efficiently interact with Vac1p and Vps45p.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332 531 WLKDDEATHCRQCEKEFSISRRKHHCRNCGHIFCN----TCSSN--------------------ELALPSYPKPVRVCDS 586
Cdd:cd15737   2 WEDDSSVTHCPICLRSFGLLLRKHHCRLCGKVVCDdrrtKCSTEvpldllssalpdlpfvfkepQSDIPDDTKSVRVCRD 81

                .
gi 94721332 587 C 587
Cdd:cd15737  82 C 82

RUN domain found in pleckstrin homology domain-containing family M member 1 (PLEKHM1) and similar proteins; PLEKHM1, also called PH domain-containing family M member 1, or 162 kDa adapter protein (AP162), may act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. This model represents the RUN domain of PLEKHM1.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332   5 RANLMHMMKLSIKVLLQSALSLGRSLDADHAPLQQFFVVMEHCLKHGLKvkKSFIGQNKSFFGPLelVEKLcPEAS---- 80
Cdd:cd17679   1 KKSLTKELSSSVKELQLEYVSSDEVVTSSDDGANTLCCVLEAIFLHGLK--DKFISKVSSVFSGD--VDKL-PEPNfwpl 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94721332  81 -------DIATSVRNLPELKTAVGRGRAWLYLALMQKKLADYLKVLIDNKHLLSEFYEPEALMMEEEGM-VIVGLLVGLN 152
Cdd:cd17679  76 llkfshrDVIDQIEHLSQITTDVGRCRAWIRLALNDGLLESYLEAILKDKSALKSYYNPSAFLRDPEQLdILKSLLQGLE 155

                ....*.
gi 94721332 153 VLDANL 158
Cdd:cd17679 156 SFQFEL 161

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 94721332 539 HCRQCEKEFSISRRKHHCRNCGHIFCNTCSSNE--LALPSYPKPVRVCDSC 587
Cdd:cd15745   1 ACAICAKAFSLFRRKYVCRLCGGVVCHSCSSEDlvLSVPDTCIYLRVCKTC 51

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and FYVE-related domain 1 found in yeast protein VAC1 (Vac1p) and similar proteins; The family includes Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and protein VAC1 (Vac1p). 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. Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The FYVE domain in both Vps27p and Vac1p harbors a zinc-binding site composed of seven Cysteines and one Histidine, which is different from that of other FYVE domain containing proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 94721332 540 CRQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSYP------KPVRVCDSC 587
Cdd:cd15736   2 CHTCSRTFNLNIRAHHCRKCGKLFCRRHLPNMIPLNLSAydprngKWYRCCHSC 55