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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568906671  17 AVSAILQGYGDGQE-PVTETSAELHRLCGCLELLLQFDQKEQRSFLGARKDYWDFLFTALRRHRGYTEQMSFICSQDKLK 95
Cdd:cd17697    5 ASIAELQKDQEEQQlPITDGSPELHRLCARLEYLLQFDQKEKKSFFGSRKDYWDFLCLCLNRHRGGTEGIHFVNSTDKLK 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568906671  96 TSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNL 161
Cdd:cd17697   85 TPLGKGRAFIRYCLVQQQLAESLQLCLLNPELTGEWYYARSPFLSPELRSDILDSLYELNGVNFDL 150

RUN domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; 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. 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; this model represents the RUN domain of RUFY4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568906671  17 AVSAILQGYGDGQE-PVTETSAELHRLCGCLELLLQFDQKEQRSFLGARKDYWDFLFTALRRHRGYTEQMSFICSQDKLK 95
Cdd:cd17697    5 ASIAELQKDQEEQQlPITDGSPELHRLCARLEYLLQFDQKEKKSFFGSRKDYWDFLCLCLNRHRGGTEGIHFVNSTDKLK 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568906671  96 TSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNL 161
Cdd:cd17697   85 TPLGKGRAFIRYCLVQQQLAESLQLCLLNPELTGEWYYARSPFLSPELRSDILDSLYELNGVNFDL 150

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 568906671  495 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS---------VDYKKRERCCPTCAQQ 540
Cdd:pfam01363  11 VCMICSKPFTFFRRRHHCRNCGRVFCSACSskkisllpeLGSNKPVRVCDACYDT 65

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 568906671   41 RLCGCLELLLQ------FDQKEQRSFLGARKDYWDFL------FTALRRHRGYTEQMSFICSqdkLKTSLGKGRAFIRLC 108
Cdd:pfam02759   1 QLCAALEALLShglkrsSLLILRAAGLLPERSFWALLervgklVPPAEELLSSVQELEQIHT---PYSPDGRGRAWIRLA 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568906671  109 LARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNLDL 163
Cdd:pfam02759  78 LNEKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGEILLGLLVGLSALDFNLCL 132

RUN domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; 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. 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; this model represents the RUN domain of RUFY4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568906671  17 AVSAILQGYGDGQE-PVTETSAELHRLCGCLELLLQFDQKEQRSFLGARKDYWDFLFTALRRHRGYTEQMSFICSQDKLK 95
Cdd:cd17697    5 ASIAELQKDQEEQQlPITDGSPELHRLCARLEYLLQFDQKEKKSFFGSRKDYWDFLCLCLNRHRGGTEGIHFVNSTDKLK 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568906671  96 TSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNL 161
Cdd:cd17697   85 TPLGKGRAFIRYCLVQQQLAESLQLCLLNPELTGEWYYARSPFLSPELRSDILDSLYELNGVNFDL 150

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 568906671  14 LKNAVSAILQGYGDGQEPvteTSAELHRLCGCLELLLQFDQKEQRSFLGARKDYWDFLFTALRRH----RGYTEQMSFIC 89
Cdd:cd17682    2 LKGCVLDLKSEFGEITDP---DNPYLRPFCETLEKILRKGLKEKVSLGGRRKDYWDWLEELLKKLnkipKSLSDAVKFVK 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568906671  90 SQDKLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNL 161
Cdd:cd17682   79 SCKKVKTNQGRGRLFIRYALNKKCLHDPVQQLVKNPKLLSDYYSPDSILGNEILSEILLSLLYQLNEINFDL 150

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 568906671  31 PVTETSAELHRLCGCLELLLQFDQKEQRSFLGARKDYWDFLFTALRRHRGYTEQMSFICSQDKLKTSLGKGRAFIRLCLA 110
Cdd:cd17681   26 TLDSDHVPLQQFFVILEHVLRHGLKVKKSFLGPNKSFWPVLEHVEKLVPEANEITASVRDLPGIKTPLGRARAWLRLALM 105

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568906671 111 RGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEdILDSLYALNGVAFNL 161
Cdd:cd17681  106 QKKLADYFRALIENKDLLSEFYEPGALMMSEEAVV-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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568906671  30 EPVTETSAELHRLCGCLELLLQFDQKEQRSFLGA--RKDYWDFLFTAlrrHRGYTEQ-MSFICSQDKLKTSLGKGRAFIR 106
Cdd:cd17684   20 ETIDDSSEELINFAAILEQILSHRLKPVKPWYGSeePRTFWDYIRVA---CKKVPQNcIASIEQMENIKSPKAKGRAWIR 96

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 568906671 107 LCLARGQLAESMQLCLLNPQLTREWYGPRSPLlcaeLQED---ILDSLYALNGVAFNL 161
Cdd:cd17684   97 VALMEKRLSEYLSTALKQTRLTRNFYQDGAIM----LSEDatvLCGMLIGLNAIDFSF 150

RUN1 domain found in DENN domain-containing protein 5 (DENND5) and similar proteins; DENND5 has been characterized as Rab6-interacting protein which is composed of an N-terminal DENN (Differentially Expressed in Normal and Neoplastic cells) domain followed by two RUN (RPIP8 [RaP2-interacting protein 8], UNC-14, and NESCA [new molecule containing SH3 at the carboxyl terminus]) domains flanking a PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain. It functions in membrane trafficking at a crossroads between the Golgi and the endosomal system. DENND5 has two isoforms, DENND5A and DENND5B. This model represents the first RUN domain of DENND5.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568906671  85 MSFICSQDKLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFN 160
Cdd:cd17677  101 MKNVQNMKEIKTDVGYARAWIRLALEKKLLSKHLKTLLSNQDLLRSLYKRYAFLRCEDEREQFLYHLLSLNAVDYF 176

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 568906671  495 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS---------VDYKKRERCCPTCAQQ 540
Cdd:pfam01363  11 VCMICSKPFTFFRRRHHCRNCGRVFCSACSskkisllpeLGSNKPVRVCDACYDT 65

RUN domain found in RUN domain-containing protein 3B (RUNDC3B) and similar proteins; RUN domain-containing protein 3B (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. RUNDC3B contains a RUN domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568906671  30 EPVTETSAELHRLCGCLELLLQFDQKEQRSFLG--ARKDYWDFLFTALRRhrgytEQMSFICS---QDKLKTSLGKGRAF 104
Cdd:cd17700   20 ETIDDSSPEFVNFAAILEQILSHRLKGQVTWFGyeSPRSFWDYIRVACSK-----VPHNCICSienMENVSSSRAKGRAW 94

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 568906671 105 IRLCLARGQLAESMQLCLLNPQLTREWYgPRSPLLCAELQEDILDSLYALNGVAFNL 161
Cdd:cd17700   95 IRVALMEKRLSEYISTALRDFKTTRRFY-EDGAIVLGEEANMLAGMLLGLNAIDFSF 150

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 568906671   495 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS--------VDYKKRERCCPTCAQ 539
Cdd:smart00064  12 NCMGCGKEFNLTKRRHHCRNCGRIFCSKCSskkaplpkLGIERPVRVCDDCYE 64

RUN1 domain found in DENN domain-containing protein 5B (DENND5B) and similar proteins; DENND5B, also called Rab6-interacting protein 1 (Rab6IP1)-like protein, functions in membrane trafficking at a crossroads between the Golgi and the endosomal system. It is composed of an N-terminal DENN (Differentially Expressed in Normal and Neoplastic cells) domain followed by two RUN (RPIP8 [RaP2-interacting protein 8], UNC-14, and NESCA [new molecule containing SH3 at the carboxyl terminus]) domains flanking a PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain. This model represents the first RUN domain of DENND5B.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568906671  83 EQMSFICSQDKLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAF 159
Cdd:cd17691  122 QDMRHIQNMSEIKTDVGRARAWIRLSLEKKLLSQHLKQLLSNQALTKKLYKRYAFLRCEEEKEQFLYHLLSLNAVDY 198

RUN domain found in pleckstrin homology domain-containing family M member 2 (PLEKHM2) and similar proteins; PLEKHM2, also called PH domain-containing family M member 2, or Salmonella-induced filaments A (SifA) and Kinesin-Interacting Protein (SKIP), is the lysosome, melanosome and lytic granule cargo adaptor that controls lysosome positioning using a composite kinesin-1 heavy and light chain-binding domain. In addition to kinesin-1, it also interacts with several Rabs to affect endosomal trafficking. This model represents the RUN domain of PLEKHM2.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568906671  12 RSLKNAVSAI--LQGY----GDGQEPVTETSAELHRLCGCLELLLQFdqkeqrSFLGARKDYWDFLFTALRRhrgytEQM 85
Cdd:cd17680    1 RILRNISEAIksLQSYsssqEEEDVLITNENRELQRLCEALDHALLH------GLRRGNRGYWPFVKEFTHK-----ETI 69

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568906671  86 SFICSQDKLKTSLGKGRAFIRLCLARGQLaES-MQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAFNL 161
Cdd:cd17680   70 KQIENLPNVTTDLGRGRAWLYLALNEGSL-ESyLRSFLENRKLVKKFYHKHALLRDSQRLELLLTLLSGLEFVQFDL 145

RUN domain found in RUN domain-containing protein 3A (RUNDC3A) and similar proteins; RUN domain-containing protein 3A (RUNDC3A), also called Rap2-interacting protein 8 (RPIP8), may act as an effector of Rap2A GTPase in neuronal cells. It contains a RUN domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568906671  17 AVSAILQGYGdgQEPVTETSAELHRLCGCLELLLQFDQKEQRSFLGA--RKDYWDFLFTALRRHRgyTEQMSFICSQDKL 94
Cdd:cd17699    9 SVKTLLEKYT--AEPIDDSSEEFVNFAAILEQILSHRFKGPVSWFSSdgQRGFWDYIRLACSKVP--NNCISSIENMENI 84

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568906671  95 KTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWY 132
Cdd:cd17699   85 STSRAKGRAWIRVALMEKRLSEYIATALRDTRTTRRFY 122

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
                 ....*....|....*....|....*....|....*....|....*....
gi 568906671 495 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS------VDYKKRERCCPTC 537
Cdd:cd15721    9 HCQQCEKEFSLSRRKHHCRNCGGIFCNSCSdntmplPSSAKPVRVCDTC 57

RUN1 domain found in DENN domain-containing protein 5A (DENND5A) and similar proteins; DENND5A, also called Rab6-interacting protein 1 (Rab6IP1), is present predominantly in developing neuronal tissue, and functions in membrane trafficking at a crossroads between the Golgi and the endosomal system. It is composed of an N-terminal DENN (Differentially Expressed in Normal and Neoplastic cells) domain followed by two RUN (RPIP8 [RaP2-interacting protein 8], UNC-14, and NESCA [new molecule containing SH3 at the carboxyl terminus]) domains flanking a PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain. This model represents the first RUN domain of DENND5A.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568906671  82 TEQMSFICSQDKLKTSLGKGRAFIRLCLARGQLAESMQLCLLNPQLTREWYGPRSPLLCAELQEDILDSLYALNGVAF 159
Cdd:cd17690  124 IQDMRHIQNIGEIKTDVGKARAWVRLSMEKKLLSRHLKQLLSDHELTKKLYKRYAFLRCDDEKEQFLYHLLSFNAVDY 201

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 568906671 495 HCIGCNKVFRRLSRRYPCRLCGGLVCHACSVD------YKKRERCCPTC 537
Cdd:cd15758   14 HCKQCEKEFSISRRKHHCRNCGHIFCNTCSSNelalpsYPKPVRVCDSC 62

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 568906671 496 CIGCNKV-FRRLSRRYPCRLCGGLVCHACS-------VDYKKRERCCPTC 537
Cdd:cd15717   11 CMHCKKTkFTAINRRHHCRKCGAVVCGACSskkfllpHQSSKPLRVCDTC 60

FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE domain-containing protein 16 (ZFY16), or endosome-associated FYVE domain protein, is a FYVE domain-containing protein that is localized to EEA1-containing endosomes. It is regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Endofin is involved in Bone morphogenetic protein (BMP) signaling through interacting with Smad1 preferentially and enhancing Smad1 phosphorylation and nuclear localization upon BMP stimulation. It also functions as a scaffold protein that brings Smad4 to the proximity of the receptor complex in Transforming growth factor (TGF)-beta signaling. Moreover, endofin is a novel tyrosine phosphorylation target downstream of epidermal growth factor receptor (EGFR) in EGF-signaling. In addition, endofin plays a role in endosomal trafficking by recruiting cytosolic TOM1, an important molecule for membrane recruitment of clathrin, onto endosomal membranes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568906671 496 CIGCNKVFRRLSRRYPCRLCGGLVCHAC-----SVDY--KKRERCCPTCAQ 539
Cdd:cd15729   16 CMQCEVKFTFTKRRHHCRACGKVLCSACcslkaRLEYldNKEARVCVPCYQ 66

FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; Lst2, also termed zinc finger FYVE domain-containing protein 28, is a monoubiquitinylated phosphoprotein that functions as a negative regulator of epidermal growth factor receptor (EGFR) signaling. Unlike other FYVE domain-containing proteins, Lst2 displays primarily non-endosomal localization. Its endosomal localization is regulated by monoubiquitinylation. Lst2 physically binds Trim3, also known as BERP or RNF22, which is a coordinator of endosomal trafficking and interacts with Hrs and a complex that biases cargo recycling.

                         10        20        30
                 ....*....|....*....|....*....|
gi 568906671 495 HCIGCNKVFRRLSRRYPCRLCGGLVCHACS 524
Cdd:cd15731   13 QCMACSAPFTVLRRRHHCRNCGKIFCSRCS 42